Therapeutic use of fibroblasts to treat the common cold

Abstract

Embodiments of the disclosure include methods and compositions for treating the common cold in an individual or one or more symptoms thereof by administering fibroblasts and / or fibroblast-derived materials to an individual in need thereof. In specific embodiments, the fibroblasts (and / or fibroblasts from which the fibroblast-derived materials are derived) express one or more specific markers. In some embodiments, the fibroblasts (and / or fibroblasts from which the fibroblast-derived materials are derived) are exposed to one or more compounds prior to use, such as exposure to Poly IC.

Description

THERAPEUTIC USE OF FIBROBLASTS TO TREAT THE COMMON COLDCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application clams the benefit of the U.S. provisional application number 63 / 602,829, filed November 27, 2023, the disclosure of which is herein incorporated by reference in its entirety.BACKGROUNDI. Technical Field

[0002] Embodiments of the disclosure concern at least the fields of cell biology, molecular biology, immunology, and medicine.II. Background

[0003] Fibroblasts are no longer considered as mere structural components of organs but as integral to the body’s healing process and regeneration of tissues. The common cold, a ubiquitous and recurring viral infection, exerts a substantial impact on public health globally. Characterized by symptoms like rhinorrhea (excess drainage, ranging from a clear fluid to thick mucus, from the nose and nasal passages), coughing, sneezing, post-nasal drip, and / or sore throat, it is primarily caused by rhinoviruses, although other respiratory viruses also contribute.

[0004] The common cold is a prevalent ailment, with adults experiencing approximately 2-3 colds annually, and children contracting even more infections per year[l]. It is primarily transmitted through respiratory droplets expelled when an infected person coughs, sneezes, or talks, as well as through direct contact with contaminated surfaces[2]. The economic burden of the common cold is considerable, with substantial healthcare costs, lost productivity, and absenteeism from work or school[3][4], A study estimated the annual economic impact of cold-related healthcare utilization and productivity losses in the United States to be over $40 billion[4]. The common cold places a strain on healthcare systems, with millions of doctor's visits annually, and contributes to the overprescription of antibiotics, despite their ineffectiveness against viral infections[5]. This leads to the misuse of healthcare resources and the development of antibiotic resistance, a pressing global health concem[6]. While usually mild in healthy adults, the common cold can have more severe consequences in infants, theelderly, and individuals with weakened immune systems, potentially leading to complications like pneumonia or exacerbation of underlying conditions[7][8],

[0005] The ease of transmission of the common cold contributes to the rapid spread of respiratory viruses within communities, particularly in crowded settings such as schools and workplaces[9]. Preventing the common cold relies on good hygiene practices, including frequent handwashing, covering coughs and sneezes, and avoiding close contact with infected individuals

[0010] . The development of vaccines for specific cold-causing viruses remains challenging, primarily because of the vast number of viral strains involved[l 1],

[0006] In conclusion, the ubiquity and transmission dynamics of the common cold make it a significant public health concern. Its economic costs, impact on healthcare systems, and potential for complications underscore the importance of preventive measures and ongoing research into effective treatments and vaccines

[0012] . Reducing the burden of the common cold can contribute to improved public health and healthcare resource allocation.SUMMARY

[0007] Embodiments of the disclosure include treatment or prevention of any illness affecting the nose and / or throat. Embodiments of the disclosure include treatment or prevention of the common cold or symptoms thereof, regardless of the cause. Embodiments of the disclosure encompass treatment of an infection of the upper respiratory tract (e.g., the nose or nostrils, nasal cavity, mouth, throat (pharynx), and / or voice box (larynx)). Embodiments of the disclosure include methods of treating infection in an individual for rhinovirus, coronavirus, parainfluenza, and / or respiratory syncytial virus (RSV). Embodiments of the disclosure include treatment or prevention of the common cold, including (regardless of infection) one or more symptoms of the common cold.

[0008] In specific embodiments, fibroblasts and / or fibroblast-derived materials may be administered to an individual having one or more symptoms of the common cold. In specific embodiments, fibroblasts and / or fibroblast-derived materials may be administered to an individual having infection by rhinovirus, coronavirus, parainfluenza, and / or RSV. In specific embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are pre-activated. In specific embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are subjected to one or more conditions that enhances their ability to treat infection by rhinovirus, coronavirus, parainfluenza, and / or RSV. In specific embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derivedmaterials are derived are subjected to one or more conditions that enhances their ability to treat one or more symptoms of the common cold. In particular embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived express one or more particular markers. In particular embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are subject to one or more compounds that enhances their ability to treat one or more symptoms of the common cold and / or enhances their ability to treat infection by rhinovirus, coronavirus, parainfluenza, and / or RSV.

[0009] Embodiments of the disclosure include methods of treating the common cold in an individual, or symptoms thereof, comprising the step of administering to the individual a therapeutically effective amount of fibroblasts and / or fibroblast-derived materials. In specific embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are autologous, allogeneic, syngeneic, or xenogeneic with respect to the individual. The fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived may express c-kit, CD105, CD73, HLA-G, TNF-alpha receptor, or a combination thereof. In specific embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived may be exposed to one or more conditions prior to the administering step. In some embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived may be pre-activated prior to the administering step. In certain embodiments, the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are subject to one or more toll-like receptor agonists, and in some cases the one or more toll-like receptor agonists comprise one or more activators of toll like receptor 3. In specific embodiments, the one or more activators of toll like receptor 3 comprise polyinosinic:polycytidylic acid (Poly IC), Polyadenylic-polyuridylic acid (Poly(AU)), poly(ICLC)(Hiltonol), RGC100, ARNAX, RIBOXXOL, or any combination thereof. In particular embodiments, the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 10 pg of interferon alpha per 1 million fibroblasts; more than 100 pg of interferon alpha per 1 million fibroblasts; more than 1 ng of interferon alpha per 1 million fibroblasts; more than 1 ng of interferon gamma per 1 million fibroblasts; more than 5 ng of interferon gamma per 1 million fibroblasts; more than 10 ng of interferon gamma per 1 million fibroblasts; more than 5 pg of interleukin-7 per 1 million fibroblasts; more than 10 pg of interleukin-7 per 1 million fibroblasts; more than 20 pg of interleukin-7 per 1 million fibroblasts; more than 15 pg of interleukin- 15 per 1 million fibroblasts; more than 30 pg of interleukin- 15 per 1 million fibroblasts; or more than 100 pg of interleukin- 15 per 1 million fibroblasts, as examples.

[0010] Any method encompassed herein may further comprise the step of isolating fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived. Specific embodiments further comprise the step of diagnosing the common cold for the individual and / or monitoring one or more symptoms of the individual. The fibroblasts and / or fibroblast- derived materials may be administered via intranasal, intravenous injection, intramuscular injection, and / or oral administration. The fibroblasts and / or fibroblast-derived materials may be lyophilized. The fibroblasts and / or fibroblast-derived materials may be configured for use as an aerosol, in a spray gun, and / or as a pump spray. Some embodiments of the disclosure encompassed methods that further comprise expanding the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived in culture prior to administering.

[0011] In certain embodiments, an individual subjected to any method encompassed herein has rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat. In some embodiments, the methods further comprise administering to the individual one or more therapies for rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat other than the fibroblasts and / or fibroblast-derived materials, such as one or more of decongestant, cough medicine, antihistamine, rest, pain reliever, increased fluid intake, and / or gargling with warm salt water. In specific embodiments, any individual subject to any method encompassed herein has rhinovirus, coronavirus, parainfluenza, and / or respiratory syncytial virus.

[0012] Embodiments of the disclosure encompasses methods of treating rhinovirus, coronavirus, parainfluenza, and / or respiratory syncytial virus in an individual, comprising the step of administering to the individual a therapeutically effective amount of fibroblasts and / or fibroblast-derived materials. In specific embodiments, the individual has rhinorrhea (excess drainage, ranging from a clear fluid to thick mucus, from the nose and nasal passages), coughing, sneezing, post-nasal drip, and / or sore throat.

[0013] Embodiments of the disclosure include methods of treating an individual, comprising the step of administering to an individual that has one or more of rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat a therapeutically effective amount of fibroblasts and / or fibroblast-derived materials.

[0014] In any of the embodiments and methods included herein, the fibroblast-derived materials may comprise exosomes, lysates, membranes, apoptotic bodies, growth factors, or any combination thereof. In some embodiments, the fibroblast-derived materials do not comprise exosomes. In some embodiments, the fibroblast-derived materials do not comprise lysates. In some embodiments, the fibroblast-derived materials do not comprise membranes.In some embodiments, the fibroblast-derived materials do not comprise apoptotic bodies. In some embodiments, the fibroblast-derived materials do not comprise growth factors.

[0015] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

[0016] Although the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions, and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the present disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.DETAILED DESCRIPTIONI. Examples of Definitions

[0017] The use of the word “a” or “an” when used in conjunction with the term “comprising” may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” In keeping with long-standing patent law convention, the words “a” and “an” when used in the present specification in concert with the word comprising, including the claims, denote “one or more.” Some embodiments of the disclosure may consist of or consist essentially of one or more elements, method steps, and / or methods of the disclosure. It is contemplated that any method or composition described herein can be implemented with respect to any other method or composition described herein.

[0018] Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the measurement or quantitation method.

[0019] The term "administered" or "administering", as used herein, refers to any method of providing a composition to an individual such that the composition has its intended effect on the patient. For example, one method of administering is by an indirect mechanism using a medical device such as, but not limited to a catheter, applicator gun, syringe etc. A second exemplary method of administering is by a direct mechanism such as, local tissue administration, oral ingestion, transdermal patch, topical, inhalation, suppository etc.

[0020] The phrase “and / or” means “and” or “or”. To illustrate, A, B, and / or C includes: A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C. In other words, “and / or” operates as an inclusive or.

[0021] As used herein, “allogeneic” refers to tissues or cells from another body that in a natural setting are immunologically incompatible or capable of being immunologically incompatible, although from one or more individuals of the same species.

[0022] As used herein, “autologous” refers to tissues or cells that are derived or transferred from the same individual's body (i.e., autologous blood donation; an autologous bone marrow transplant).

[0023] As used herein, “xenogeneic” refers to tissues or cells from a species different from the patient.

[0024] Cell culture" is an artificial in vitro system containing viable cells, whether quiescent, senescent or (actively) dividing. In a cell culture, cells are grown and maintained at an appropriate temperature, typically a temperature of 37°C and under an atmosphere typically containing oxygen and CO2. Culture conditions may vary widely for each cell type though, and variation of conditions for a particular cell type can result in different phenotypes being expressed. The most commonly varied factor in culture systems is the growth medium. Growth media can vary in concentration of nutrients, growth factors, and the presence of other components. The growth factors used to supplement media are often derived from animal blood, such as calf serum.

[0025] Throughout this specification, unless the context requires otherwise, the words “comprise”, “comprises” and “comprising” will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements. By “consisting of’ is meant including, and limited to, whatever follows the phrase “consisting of.” Thus, the phrase “consisting of’ indicates that the listed elements are required or mandatory, and that no other elements may be present. By “consisting essentially of’ is meant including any elements listed after the phrase and limited to otherelements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of’ indicates that the listed elements are required or mandatory, but that no other elements are optional and may or may not be present depending upon whether or not they affect the activity or action of the listed elements.

[0026] The term "individual", as used herein, refers to a human or animal that may or may not be housed in a medical facility and may be treated as an outpatient of a medical facility. The individual may be receiving one or more medical compositions via the internet. An individual may comprise any age of a human or non-human animal and therefore includes both adults and juveniles (i.e., children) and infants. It is not intended that the term "individual" connotes a need for medical treatment, therefore, an individual may voluntarily or involuntarily be part of experimentation whether clinical or in support of basic science studies. The term “subject” or “individual” may be used interchangeably and refers to any organism or animal subject that is an object of a method or material, including mammals, e.g., humans, laboratory animals (e.g., primates, rats, mice, rabbits), livestock (e.g., cows, sheep, goats, pigs, turkeys, and chickens), household pets (e.g., dogs, cats, and rodents), horses, and transgenic non-human animals.

[0027] Reference throughout this specification to “one embodiment,” “an embodiment,” “a particular embodiment,” “a related embodiment,” “a certain embodiment,” “an additional embodiment,” or “a further embodiment” or combinations thereof means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of the foregoing phrases in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0028] Treatment,” “treat,” or “treating” means a method of reducing the effects of a disease or condition. Treatment can also refer to a method of reducing the disease or condition itself rather than just the symptoms. The treatment can be any reduction from pre-treatment levels and can be but is not limited to the complete ablation of the disease, condition, or the symptoms of the disease or condition. Therefore, in the disclosed methods, “treatment” can refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of an established disease or the disease progression, including reduction in the severity of at least one symptom of the disease . For example, a disclosed method for reducing the immunogenicity of cells is considered to be a treatment if there is a detectable reduction in theimmunogenicity of cells when compared to pre-treatment levels in the same subject or control subjects . Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels . It is understood and herein contemplated that “treatment” does not necessarily refer to a cure of the disease or condition, but an improvement in the outlook of a disease or condition. In specific embodiments, treatment refers to the lessening in severity or extent of at least one symptom and may alternatively or in addition refer to a delay in the onset of at least one symptom.

[0029] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the invention, and vice versa. Furthermore, compositions of the disclosure can be used to achieve methods of the disclosure.II. General Embodiments

[0030] The present disclosure relates to novel methods and compositions for treating the common cold, including using fibroblasts and / or fibroblast-derived materials for treating the common cold. In some embodiments, fibroblasts and / or fibroblast-derived compositions are utilized for treating one or more symptoms of the common cold, regardless of whether or not the symptoms are caused directly or indirectly by any virus that causes the common cold. Examples of symptoms that may be treated with fibroblasts and / or fibroblast-derived materials include at least rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat, regardless of whether or not the symptoms are caused directly or indirectly by a virus that causes the common cold.

[0031] In specific embodiments, the method involves the administration of fibroblasts and / or fibroblast-derived compositions to alleviate one or more symptoms of the common cold, to reduce viral replication, and / or to expedite recovery from the common cold. In particular embodiments, the method utilizes specialized compositions of fibroblast-derived materials, such as exosomes, lysates, membranes, apoptotic bodies, and / or growth factors. In some embodiments, the fibroblast-derived materials do not comprise exosomes (e.g., may comprise lysates, membranes, apoptotic bodies, and / or growth factors). In some embodiments, the fibroblast-derived materials do not comprise lysates (e.g., may comprise exosomes, membranes, apoptotic bodies, and / or growth factors). In some embodiments, the fibroblast- derived materials do not comprise membranes (e.g., may comprise exosomes, lysates, apoptotic bodies, and / or growth factors). In some embodiments, the fibroblast-derived materials do not comprise apoptotic bodies (e.g., may comprise exosomes, lysates, membranes, and / or growthfactors). In some embodiments, the fibroblast-derived materials do not comprise growth factors (e.g., may comprise exosomes, lysates, membranes, and / or apoptotic bodies). In specific embodiments, this system significantly enhances eradication of one or more symptoms and facilitates recovery time. In specific embodiments, one could utilize an aerosol, pump spray, or spray gun to apply the mixture via intranasal application. In some embodiments, the fibroblasts and / or fibroblast-derived materials could be injected into the individual, such as intravenously or intramuscular.

[0032] Using fibroblasts and / or fibroblast-derived materials to treat the common cold is a novel approach with multiple benefits. Advantages of using fibroblasts and / or fibroblast- derived materials for common cold treatment include the following:

[0033] Reduced Symptom Severity: in specific embodiments, fibroblasts and / or fibroblast- derived materials have immunomodulatory properties that help reduce the severity of one or more common cold symptoms, such as rhinorrhea (excess drainage, ranging from a clear fluid to thick mucus, from the nose and nasal passages), nasal congestion, coughing, sneezing, postnasal drip, and / or sore throat.

[0034] Accelerated Recovery: in specific embodiments, fibroblasts and / or fibroblast- derived materials speed up the body’s natural healing process, allowing individuals to recover from the common cold more quickly.

[0035] Antiviral Effects: in specific embodiments, fibroblasts and / or fibroblast-derived materials have antiviral properties, helping to inhibit the replication of the cold virus in the body.

[0036] Fewer Side Effects: Compared to some conventional cold treatments, such as certain antiviral medications, fibroblasts and / or fibroblast-derived materials have fewer side effects (e.g., drowsiness, dizziness, blurred vision, upset stomach, nausea, nervousness, constipation, or dry mouth / nose / throat).

[0037] Use for Personalized Medicine: In specific embodiments, fibroblasts and / or fibroblast-derived materials are customized based on a patient’s unique immune profile, allowing for more tailored treatment approaches.

[0038] Immune System Support: In some embodiments, fibroblasts boost the overall immune response, providing better protection against future colds or future exposure to viruses that cause the common cold.

[0039] Embodiments of the disclosure include methods for treating the common cold in an individual comprising the step(s) of (a) optionally isolating autologous, allogeneic, syngeneic, or xenogeneic fibroblasts (or a mixture thereof) from a suitable source; (b) optionallygenerating fibroblasts and / or fibroblast-derived materials; (c) administering fibroblasts and / or fibroblast-derived materials to an individual in need thereof; and (d) optionally monitoring the recovery and / or symptoms of the individual. In particular embodiments, the individual may or may not have been diagnosed with the common cold. In some embodiments, the fibroblasts and / or fibroblast-derived materials are administered via intranasal, intravenous injection, intramuscular injection, or oral administration. In some embodiments, the fibroblasts and / or fibroblast-derived materials are lyophilized for use in aerosol, spray gun, and / or pump spray. The fibroblasts and / or fibroblast-derived materials and / or any administration equipment may be provided by means of a kit.

[0040] Embodiments of the disclosure include compositions for treating the common cold or symptoms of the common cold, said composition comprising isolated fibroblasts and / or fibroblast-derived materials. In embodiments of methods and / or compositions, the fibroblasts (and / or fibroblasts from which the fibroblast-derived materials are derived) are cultured and expanded, e.g., to increase their therapeutic potential.

[0041] Embodiments of the disclosure include fibroblasts and / or fibroblast-derived materials that are customized based on a patient’s unique immune profile, allowing for more tailored treatment approaches.

[0042] In particular embodiments, fibroblasts (and / or fibroblasts from which the fibroblast- derived materials are derived) areolated for enhanced therapeutic properties. In specific embodiments, the enhanced therapeutic properties are selected from the group consisting of a) interferon secretion; b) ability to enhance cell-mediated cytotoxicity; c) ability to stimulate natural killer cell activity; d) ability to enhance antigen presentation; e) ability to suppress viral replication; and f) a combination thereof. In specific embodiments, the fibroblasts (and / or fibroblasts from which the fibroblast-derived materials are derived) areolated by selection for the expression of one or more markers. In specific embodiments, the fibroblasts (and / or fibroblasts from which the fibroblast-derived materials are derived) are selected for expression of c-kit, CD105, CD73, HLA-G, TNF-alpha receptor, or a combination thereof.

[0043] In particular embodiments, the fibroblasts (and / or fibroblasts from which the fibroblast-derived materials are derived) are subject to one or more specific conditions and / or one or more specific compounds. In specific embodiments, the fibroblasts are pre-activated with one or more toll like receptor agonists. In certain embodiments, the one or more toll like receptor agonists comprise one or more activators of toll like receptor 3. In certain embodiments, the one or more activators of toll like receptor 3 comprise Polyinosinic:polycytidylic acid (Poly IC), Polyadenylic-polyuridylic acid (Poly(AU)),poly(ICLC)(Hiltonol), RGC100, ARNAX, RIBOXXOL, or any combination thereof. Poly IC is a mismatched double-stranded RNA comprising two strands where one is a polymer of inosinic acid and the other is a polymer of cytidylic acid. Poly AU is the same but where one strand is a polymer of adenylic acid and the other is polyuridylic acid, poly (ICLC) or “Hiltonol” is poly IC (polyinosinic-polycytidylic acid) with stabilizers carboxymethylcellulose and polylysine. RGC100 is a nucleic acid based agonist described in Naumann, Kai, et al. "Activation of Dendritic Cells by the Novel Toll-Like Receptor 3 Agonist RGC100." Journal of Immunology Research 2013.1 (2013): 283649, which is incorporated herein by reference in its entirety. ARNAX is DNA capped dsRNA that specifies the endosomal target for Toll-like receptor 3 (TLR3) in dendritic cells (see e.g., Seya T, et al., “A Toll-like receptor 3 (TLR3) agonist ARNAX for therapeutic immunotherapy.” Adv Drug Deliv Rev. 2019 Jul;147:37-43, incorporated herein by reference in its entirety). RIBOXXOL (RIBOXX RNA TECHNOLOGIES) is a synthetic double stranded RNA comprised of cytosines, inosines, and guanosines.

[0044] In some embodiments, the one or more activators of toll like receptor 3 (e.g., Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are subjected to fibroblasts at a concentration and time period sufficient to induce production of more than 10 pg of interferon alpha per 1 million fibroblasts. In specific embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 100 pg of interferon alpha per 1 million fibroblasts. In specific embodiments, the one or more activators of toll like receptor 3 (e.g., Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 1 ng of interferon alpha per 1 million fibroblasts. In some embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 1 ng of interferon gamma per 1 million fibroblasts. In specific embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 5 ng of interferon gamma per 1 million fibroblasts. In specific embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 10 ng of interferon gamma per 1 millionfibroblasts. In some embodiments, the one or more activators of toll like receptor 3 (e.g., Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 5 pg of interleukin-7 per 1 million fibroblasts. In some embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 10 pg of interleukin-7 per 1 million fibroblasts. In some embodiments, the one or more activators of toll like receptor 3 (e.g., Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 20 pg of interleukin-7 per 1 million fibroblasts. In specific embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 15 pg of interleukin- 15 per 1 million fibroblasts. In some embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 30 pg of interleukin- 15 per 1 million fibroblasts. In specific embodiments, the one or more activators of toll like receptor 3 (e.g. Poly IC, Poly AU, Poly ICLC, RGC100, ARNAX, or RIBOXXOL) are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 100 pg of interleukin- 15 per 1 million fibroblasts.

[0045] In some embodiments, any individual that is administered any composition(s) encompassed herein may be of any age, including at least (or no more than) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, or greater in age. The individual may be a newborn, an infant, a child, an adolescent, or an adult. The individual may be infants, young children, and elderly who have a greater risk of colds than other people. The individual may or may have a weakened immune system. The individual may or may not have a chronic illness or a long-term illness. The individual may be administered any composition encompassed herein at a certain time of year, such as during fall and / or winter. The individual may be a smoker. In some embodiments, the individual is exposed (including routinely or substantially constantly) to an environment or facility with large numbers of people, such as achild care setting, hospital, nursing home, medical facility, hospital, elderly care facility, skilled nursing facility, school, airplane, cruise ship, train, sports arena, and so forth.

[0046] In certain embodiments, the individual is at risk for developing one or more other medical conditions as a result of having the common cold, or the individual has developed one or more other medical conditions as a result of having the common cold. For example, the individual is at risk of having, or has developed, middle ear infection; asthma; sinusitis; pneumonia; bronchitis, or a combination thereof.

[0047] In particular embodiments, any composition encompassed herein may be utilized for an individual to prevent the common cold or reduce the risks of getting the common cold or reduce the severity of one or more symptoms of the common cold or delay the onset of the common cold. In some embodiments, any composition encompassed herein reduces or eliminates or prevents one or more symptoms of the common cold. In specific embodiments, any composition encompassed herein reduces or eliminates or prevents rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat. In particular embodiments, one or more compositions encompassed herein reduces the ability of one individual with the common cold to infect another individual.

[0048] In embodiments of the disclosure, any method of the disclosure may have one or more of the following steps: administering fibroblasts to an individual; administering fibroblast-derived materials to an individual; administering fibroblasts and fibroblast-derived materials to an individual; diagnosing or ascertaining one or more symptoms of the common cold; diagnosing or ascertaining rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat in an individual; determining the presence of rhinovirus, coronavirus, parainfluenza, and / or RSV in an individual; administering one or more additional therapies for rhinovirus, coronavirus, parainfluenza, and / or RSV other than fibroblasts and / or fibroblast-derived materials; expanding fibroblasts in culture; identifying or selecting for fibroblasts that express one or more of c-kit, CD105, CD73, HLA-G, and TNF-alpha receptor; exposing fibroblasts and / or fibroblasts from which fibroblast-derived materials are obtained to one or more particular conditions; exposing fibroblasts and / or fibroblasts from which fibroblast-derived materials are obtained to a pre-activating step; exposing fibroblasts and / or fibroblasts from which fibroblast-derived materials are obtained to an effective amount of one or more toll-like receptor agonists; exposing fibroblasts and / or fibroblasts from which fibroblast-derived materials are obtained to an effective amount of Poly IC; and so forth.III. The Common Cold

[0049] Embodiments of the disclosure concern treatment of the common cold in an individual. Embodiments of the disclosure concern treatment of one or more symptoms of the common cold, regardless of whether or not the individual is infected with one or more pathogens that cause the common cold, including one or more viruses. In specific embodiments, the individual may or may not have been diagnosed by a medical practitioner with having one or more viruses that cause the common cold. In specific embodiments, the individual may or may not have been diagnosed by a medical practitioner with having one or more symptoms indicative of the common cold. In some embodiments the individual has 1, 2, 3, 4, or all of the following: rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat. The individual symptoms may or may not have a substantially same onset for the individual. The individual may or may not have fever. The individual may be uncertain of having the common cold vs. influenza infection. Any composition encompassed herein may be provided in an over-the-counter setting.

[0050] In some embodiments, the individual has rhinovirus, coronavirus, parainfluenza, and / or RSV, each of which may be associated with one or more common cold symptoms. Any compositions encompassed herein may treat a viral infection that directly or indirectly causes common cold symptom(s), and / or any compositions encompassed herein may treat one or more common cold symptom(s) but does not treat the viral infection directly or indirectly related to the symptoms. In specific embodiments, any composition encompassed herein inhibits the replication of any virus that directly or indirectly causes common cold symptoms, such as inhibiting the replication of rhinovirus, coronavirus, parainfluenza, and / or RSV.IV. Administration of Therapeutic Compositions

[0051] Embodiments of the present disclosure include administering therapeutic compositions to an individual in need thereof comprising fibroblasts and / or fibroblast-derived materials. The therapeutic compositions may be administered by the affected individual rather than a medical practitioner and / or they may be administered to the individual by a medical practitioner. The therapy provided herein may comprise administration of a combination of therapeutic agents that may or may not be in the same formulation. One or more therapies other than fibroblasts and / or fibroblast-derived materials may comprise one or more ofdecongestant, cough medicine, antihistamine, rest, pain reliever, increased fluid intake, and / or gargling with warm salt water. The separate therapies may be administered in any suitable manner known in the art. For example, the treatments may be administered sequentially (at different times) or concurrently (at the same time or at substantially the same time). In some embodiments, the separate treatments are administered in a separate composition or formulation. In some embodiments, the separate treatments are in the same composition or formulation.

[0052] The separate therapeutic agents of the disclosure may be administered by the same route of administration or by different routes of administration. In some embodiments, one therapy is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally. In some embodiments, another therapy is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally. The appropriate dosage may be determined based on the type of disease to be treated, severity and course of the disease, the clinical condition of the individual, the individual's clinical history and response to the treatment, and the discretion of the attending physician.

[0053] The treatments may include various “unit doses.” Unit dose is defined as containing a predetermined-quantity of the therapeutic composition. The quantity to be administered, and the particular route and formulation, is within the skill of determination of those in the clinical arts. A unit dose need not be administered as a single injection but may comprise continuous infusion over a set period of time. In some embodiments, a unit dose comprises a single administrable dose.

[0054] In some embodiments, the fibroblasts and / or fibroblast-derived materials are administered at a dose of between 1 mg / kg and 5000 mg / kg. In some embodiments, the fibroblasts and / or fibroblast-derived materials are administered at a dose of at least, at most, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120,121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139,140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158,159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177,178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215,216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234,235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272,273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291,292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329,330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348,349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367,368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386,387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443,444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481,482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500,501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519,520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538,539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557,558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 600, 700, 800, 900,1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, or 5000 mg / kg.

[0055] The quantity to be administered, both according to number of treatments and unit dose, depends on the treatment effect desired. An effective dose is understood to refer to an amount necessary to achieve a particular effect. In the practice in certain embodiments, it is contemplated that doses in the range from 10 mg / kg to 200 mg / kg can affect the protective capability of these agents. Thus, it is contemplated that doses include doses of about 0.1, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, and 200, 300, 400, 500, 1000 pg / kg, mg / kg, pg / day, or mg / day or any range derivable therein. Furthermore, suchdoses can be administered at multiple times during a day, and / or on multiple days, weeks, or months.

[0056] In certain embodiments, the effective dose of the pharmaceutical composition is one which can provide a blood level of about 1 pM to 150 pM. In another embodiment, the effective dose provides a blood level of about 4 pM to 100 pM.; or about 1 pM to 100 pM; or about 1 pM to 50 pM; or about 1 pM to 40 pM; or about 1 pM to 30 pM; or about 1 pM to 20 pM; or about 1 pM to 10 pM; or about 10 pM to 150 pM; or about 10 pM to 100 pM; or about 10 pM to 50 pM; or about 25 pM to 150 pM; or about 25 pM to 100 pM; or about 25 pM to 50 pM; or about 50 pM to 150 pM; or about 50 pM to 100 pM (or any range derivable therein). In other embodiments, the dose can provide the following blood level of the agent that results from a therapeutic agent being administered to a subject: about, at least about, or at most about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 pM or any range derivable therein. In certain embodiments, the therapeutic agent that is administered to a subject is metabolized in the body to a metabolized therapeutic agent, in which case the blood levels may refer to the amount of that agent. Alternatively, to the extent the therapeutic agent is not metabolized by a subject, the blood levels discussed herein may refer to the unmetabolized therapeutic agent.

[0057] Precise amounts of the therapeutic composition also depend on the judgment of the practitioner and are peculiar to each individual. Factors affecting dose include physical and clinical state of the patient, the route of administration, the intended goal of treatment (alleviation of symptoms versus cure) and the potency, stability and toxicity of the particular therapeutic substance or other therapies a subject may be undergoing.

[0058] It will be understood by those skilled in the art and made aware that dosage units of pg / kg or mg / kg of body weight can be converted and expressed in comparable concentration units of pg / ml or mM (blood levels), such as 4 pM to 100 pM. It is also understood that uptake is species and organ / tissue dependent. The applicable conversion factors and physiological assumptions to be made concerning uptake and concentration measurement are well-known and would permit those of skill in the art to convert one concentration measurement to another and make reasonable comparisons and conclusions regarding the doses, efficacies and results described herein.

[0059] In certain instances, it will be desirable to have multiple administrations of the composition, e.g., 2, 3, 4, 5, 6 or more administrations. The administrations can be at 1, 2, 3, 4, 5, 6, 7, 8, to 5, 6, 7, 8, 9, 10, 11, or 12 week intervals, including all ranges there between.

[0060] The phrases “pharmaceutically acceptable” or “pharmacologically acceptable” refer to molecular entities and compositions that do not produce an adverse, allergic, or other untoward reaction when administered to an animal or human. As used herein, “pharmaceutically acceptable carrier” includes any and all solvents, dispersion media, coatings, anti-bacterial and anti-fungal agents, isotonic and absorption delaying agents, and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredients, its use in immunogenic and therapeutic compositions is contemplated. Supplementary active ingredients, such as other anti-infective agents and vaccines, can also be incorporated into the compositions.

[0061] The active compounds can be formulated for parenteral administration, e.g., formulated for injection via the intravenous, intramuscular, subcutaneous, or intraperitoneal routes. Typically, such compositions can be prepared as either liquid solutions or suspensions; solid forms suitable for use to prepare solutions or suspensions upon the addition of a liquid prior to injection can also be prepared; and, the preparations can also be emulsified.

[0062] The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions; formulations including, for example, aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases the form must be sterile and must be fluid to the extent that it may be easily injected. It also should be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi.

[0063] The proteinaceous compositions may be formulated into a neutral or salt form. Pharmaceutically acceptable salts, include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, histidine, procaine and the like.

[0064] A pharmaceutical composition can include a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, andliquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion, and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various anti-bacterial and anti-fungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0065] Sterile injectable solutions are prepared by incorporating the active compounds in the required amount in the appropriate solvent with various other ingredients enumerated above, as required, followed by filtered sterilization or an equivalent procedure. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying techniques, which yield a powder of the active ingredient, plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0066] Administration of the compositions will typically be via any common route. This includes, but is not limited to oral, or intravenous administration. Alternatively, administration may be by orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal, or intranasal administration. Such compositions would normally be administered as pharmaceutically acceptable compositions that include physiologically acceptable carriers, buffers or other excipients.

[0067] Upon formulation, solutions will be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically or prophylactically effective. The formulations are easily administered in a variety of dosage forms, such as the type of injectable solutions described above.

[0068] In certain aspects, the compositions or agents for use in the methods, such as fibroblasts and / or fibroblast-derived materials, are suitably contained in a pharmaceutically acceptable carrier. The carrier is non-toxic, biocompatible and is selected so as not to detrimentally affect the biological activity of the agent. The agents in some aspects of the disclosure may be formulated into preparations for local delivery (i.e. to a specific location of the body, such as the upper respiratory tract, sinus cavities, nose, or other tissue) or systemicdelivery, in solid, semi-solid, gel, liquid or gaseous forms such as tablets, capsules, powders, granules, ointments, solutions, depositories, inhalants and injections allowing for oral, parenteral or surgical administration. Certain aspects of the disclosure also contemplate local administration of the compositions by coating medical devices and the like.

[0069] Suitable carriers for parenteral delivery via injectable, infusion or irrigation and topical delivery include distilled water, physiological phosphate-buffered saline, normal or lactated Ringer's solutions, dextrose solution, Hank's solution, or propanediol. In addition, sterile, fixed oils may be employed as a solvent or suspending medium. For this purpose any biocompatible oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. The carrier and agent may be compounded as a liquid, suspension, polymerizable or non-polymerizable gel, paste or salve.

[0070] The carrier may also comprise a delivery vehicle to sustain (i.e., extend, delay or regulate) the delivery of the agent(s) or to enhance the delivery, uptake, stability or pharmacokinetics of the therapeutic agent(s). Such a delivery vehicle may include, by way of non-limiting examples, microparticles, microspheres, nanospheres or nanoparticles composed of proteins, liposomes, carbohydrates, synthetic organic compounds, inorganic compounds, polymeric or copolymeric hydrogels and polymeric micelles.

[0071] In certain aspects, the actual dosage amount of a composition administered to a patient or subject can be determined by physical and physiological factors such as body weight, severity of condition, the type of disease being treated, previous or concurrent therapeutic interventions, idiopathy of the patient and on the route of administration. The practitioner responsible for administration will, in any event, determine the concentration of active ingredient(s) in a composition and appropriate dose(s) for the individual subject.

[0072] Solutions of pharmaceutical compositions can be prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions also can be prepared in glycerol, liquid polyethylene glycols, mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

[0073] In certain aspects, the pharmaceutical compositions are advantageously administered in the form of injectable compositions either as liquid solutions or suspensions; solid forms suitable or solution in, or suspension in, liquid prior to injection may also be prepared. These preparations also may be emulsified. A typical composition for such purpose comprises a pharmaceutically acceptable carrier. For instance, the composition may contain10 mg or less, 25 mg, 50 mg or up to about 100 mg of human serum albumin per milliliter of phosphate buffered saline. Other pharmaceutically acceptable carriers include aqueous solutions, non-toxic excipients, including salts, preservatives, buffers and the like.

[0074] Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oil and injectable organic esters such as ethyloleate. Aqueous carriers include water, alcoholic / aqueous solutions, saline solutions, parenteral vehicles such as sodium chloride, Ringer's dextrose, etc. Intravenous vehicles include fluid and nutrient replenishers. Preservatives include antimicrobial agents, antgifungal agents, anti-oxidants, chelating agents and inert gases. The pH and exact concentration of the various components the pharmaceutical composition are adjusted according to well-known parameters.

[0075] Additional formulations are suitable for oral administration. Oral formulations include such typical excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate and the like. The compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders.

[0076] In further aspects, the pharmaceutical compositions may include classic pharmaceutical preparations. Administration of pharmaceutical compositions according to certain aspects may be via any common route so long as the target tissue is available via that route. This may include oral, nasal, buccal, rectal, vaginal or topical. Alternatively, administration may be by orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal or intravenous injection. Such compositions would normally be administered as pharmaceutically acceptable compositions that include physiologically acceptable carriers, buffers or other excipients. For treatment of conditions of the lungs, aerosol delivery can be used. Volume of the aerosol may be between about 0.01 ml and 0.5 ml, for example.

[0077] An effective amount of the pharmaceutical composition is determined based on the intended goal. The term “unit dose” or “dosage” refers to physically discrete units suitable for use in a subject, each unit containing a predetermined-quantity of the pharmaceutical composition calculated to produce the desired responses discussed above in association with its administration, i.e., the appropriate route and treatment regimen. The quantity to be administered, both according to number of treatments and unit dose, depends on the protection or effect desired.

[0078] Precise amounts of the pharmaceutical composition also depend on the judgment of the practitioner and are peculiar to each individual. Factors affecting the dose include the physical and clinical state of the patient, the route of administration, the intended goal oftreatment (e.g., alleviation of symptoms versus cure) and the potency, stability and toxicity of the particular therapeutic substance.* * *

[0079] All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.REFERENCESThe following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.

[0080] 1. Heikkinen, T., & Jarvinen, A. (2003). The common cold. The Lancet,361(9351), 51-59.

[0081] 2. Turner, R. B. (2007). Rhinovirus: More than just a common cold virus. Journal of Infectious Diseases, 195(6), 765-766.

[0082] 3. Fendrick, A. M., Monto, A. S., & Nightengale, B. (2003). The economic burden of non-influenza-related viral respiratory tract infection in the United States. Archives of Internal Medicine, 163(4), 487-494.

[0083] 4. Smith, A. P., Thomas, M., & Brockman, P. (2017). The cost of fever and fever- related symptoms to an employer: A pilot study. British Journal of Nutrition, 116(4), 766-770.

[0084] 5. King, L. M., Fleming-Dutra, K. E., Hicks, L. A., & Advances in the prevention and control of infectious diseases. (2018). Antibiotic prescribing for the treatment of upper respiratory infections among children in primary care: A systematic review. The Journal of Pediatrics, 203, 241-249.

[0085] 6. Ventola, C. L. (2015). The antibiotic resistance crisis: Part 1 : Causes and threats.P & T: A Peer-Reviewed Journal for Formulary Management, 40(4), 277-283.

[0086] 7. Eccles, R. (2005). Understanding the symptoms of the common cold and influenza. The Lancet Infectious Diseases, 5(11), 718-725.

[0087] 8. Monto, A. S. (2002). The seasonality of rhinovirus infections and its implications for clinical recognition. Clinical Therapeutics, 24(12), 1987-1997.

[0088] 9. Tellier, R. (2006). Review of aerosol transmission of influenza A virus.Emerging Infectious Diseases, 12(11), 1657-1662.

[0089] 10. Jefferson, T., Del Mar, C. B., Dooley, L., Ferroni, E., Al-Ansary, L. A.,Bawazeer, G. A., ... & Jones, M. A. (2011). Physical interventions to interrupt or reduce the spread of respiratory viruses: Systematic review. Bmj, 343, d4801.

[0090] 11. Schmidt, A. C. (2018). Progress in the development of human rhinovirus therapeutics and vaccines. The Journal of Infectious Diseases, 218(6), 874-881.

[0091] 12. Prasso, J. E., & Deng, X. (2018). Progress in developing inhibitors of human rhinovirus 3C protease. Future Medicinal Chemistry, 10(7), 775-794.

Claims

WHAT IS CLAIMED IS:

1. A method of treating the common cold in an individual, or symptoms thereof, comprising the step of administering to the individual a therapeutically effective amount of fibroblasts and / or. fibroblast-derived materials.

2. The method of claim 1, wherein the fibroblasts and / or fibroblasts from which the fibroblast- derived materials are derived are autologous, allogeneic, syngeneic, or xenogeneic with respect to the individual.

3. The method of claim 1 or 2, wherein the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived express c-kit, CD105, CD73, HLA-G, TNF-alpha receptor, or a combination thereof.

4. The method of any one of the preceding claims, wherein the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are exposed to one or more conditions prior to the administering step.

5. The method of any one of the preceding claims, wherein the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived are pre-activated prior to the administering step.

6. The method of claim 5, wherein the fibroblasts and / or fibroblasts from which the fibroblast- derived materials are derived are subject to one or more toll-like receptor agonists.

7. The method of claim 6, wherein the one or more toll-like receptor agonists comprise one or more activators of toll like receptor 3.

8. The method of claim 7, wherein one or more activators of toll like receptor 3 comprise polyinosinic:polycytidylic acid (Poly IC), Polyadenylic-polyuridylic acid (Poly(AU)), poly(ICLC)(Hiltonol), RGC100, ARNAX, RIBOXXOL, or any combination thereof.

9. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 10 pg of interferon alpha per 1 million fibroblasts.

10. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 100 pg of interferon alpha per 1 million fibroblasts.

11. The method of claim 8, the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 1 ng of interferon alpha per 1 million fibroblasts.

12. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 1 ng of interferon gamma per 1 million fibroblasts.

13. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 5 ng of interferon gamma per 1 million fibroblasts.

14. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 10 ng of interferon gamma per 1 million fibroblasts.

15. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 5 pg of interleukin-7 per 1 million fibroblasts.

16. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 10 pg of interleukin-7 per 1 million fibroblasts.

17. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 20 pg of interleukin-7 per 1 million fibroblasts.

18. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 15 pg of interleukin- 15 per 1 million fibroblasts.

19. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 30 pg of interleukin- 15 per 1 million fibroblasts.

20. The method of claim 8, wherein the one or more activators of toll like receptor 3 are administered to fibroblasts at a concentration and time period sufficient to induce production of more than 100 pg of interleukin- 15 per 1 million fibroblasts.

21. The method of any one of the preceding claims, further comprising the step of isolating fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived.

22. The method of any one of the preceding claims, further comprising the step of diagnosing the common cold for the individual.

23. The method of any one of the preceding claims, further comprising the step of monitoring one or more symptoms of the individual.

24. The method of any one of the preceding claims, wherein the fibroblasts and / or fibroblast- derived materials are administered via intranasal, intravenous injection, intramuscular injection, or oral administration.

25. The method of any one of the preceding claims, wherein the fibroblasts and / or fibroblast- derived materials are lyophilized.

26. The method of any one of the preceding claims, wherein the fibroblasts and / or fibroblast- derived materials are configured for use as an aerosol, in a spray gun, and / or as a pump spray.

27. The method of any one of the preceding claims, further comprising expanding the fibroblasts and / or fibroblasts from which the fibroblast-derived materials are derived in culture prior to administering.

28. The method of any one of the preceding claims, wherein the individual has rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat.

29. The method of any one of the preceding claims, further comprising administering to the individual one or more therapies other than the fibroblasts and / or fibroblast-derived materials for rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat.

30. The method of claim 29, wherein the one or more therapies comprise one or more of decongestant, cough medicine, antihistamine, rest, pain reliever, increased fluid intake, and / or gargling with warm salt water.

31. The method of any one of the preceding claims, wherein the individual has rhinovirus, coronavirus, parainfluenza, and / or respiratory syncytial virus.

32. A method of treating rhinovirus, coronavirus, parainfluenza, and / or respiratory syncytial virus in an individual, comprising the step of administering to the individual a therapeutically effective amount of fibroblasts and / or fibroblast-derived materials.

33. The method of claim 32, wherein the individual has rhinorrhea (excess drainage, ranging from a clear fluid to thick mucus, from the nose and nasal passages), coughing, sneezing, post-nasal drip, and / or sore throat.

34. A method of treating an individual, comprising the step of administering to an individual that has one or more of rhinorrhea, coughing, sneezing, post-nasal drip, and / or sore throat a therapeutically effective amount of fibroblasts and / or fibroblast-derived materials.

35. The method of any one of the preceding claims wherein the fibroblast-derived materials comprise exosomes, lysates, membranes, apoptotic bodies, growth factors, or any combination thereof.

36. The method of claim 35, wherein the fibroblast-derived materials do not comprise exosomes.

37. The method of claim 35, wherein the fibroblast-derived materials do not comprise lysates.

38. The method of claim 35, wherein the fibroblast-derived materials do not comprise membranes.

39. The method of claim 35, wherein the fibroblast-derived materials do not comprise apoptotic bodies.

40. The method of claim 35, wherein the fibroblast-derived materials do not comprise growth factors.