359 results about "Organ transplantation" patented technology

The present invention relates to utrons, RNA molecules which contain promoter regulatory motif(s) and DNA analogs thereof and DNA molecules that can be transcribed to produce the foregoing. In particular, the invention provides gene promoter suppressing nucleic acids which suppress transcription from a promoter of interest. In a preferred embodiment, the invention provides the TSU gene, nucleotide sequences of the TSU gene and RNA, as well as fragments, homologs and derivatives thereof. Methods of isolating TSU genes are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are also provided. In particular, the invention relates to methods for cell replacement therapy, gene therapy or organ transplantation wherein TSU nucleic acids suppress MHC class I and II gene expression, thus preventing immuno-rejection of non-autologous cells or organs. The invention also provides methods for treatment of diseases or disorders by suppression of MHC class I, MHC class II, ICAM-1, B7-1, B7-2, and / or Fc gamma R expression by provision of TSU function.

Methods are provided for evaluating a subject for graft survival, e.g., in terms of predicting graft survival, identifying the presence of a deleterious graft condition, such as CAN and DT, identifying the severity and class of acute rejection, etc, in a subject are provided. In practicing the subject methods, the expression of at least one gene in a sample from the subject, e.g., a blood or biopsy sample, is assayed, e.g., at the nucleic acid and / or protein level, to evaluate the subject. Also provided are compositions, systems and kits that find use in practicing the subject methods. The methods and compositions find use in a variety of applications.

The present inventors assessed the effect of anti-IL-6 receptor antibodies in suppressing chronic rejection reaction. They assessed the effect of anti-mouse IL-6 receptor antibody (MR16-1) administration in suppressing the chronic rejection reaction using a mouse model for post-heart-transplantation chronic rejection. The result of histopathological analysis of transplanted hearts extirpated 60 days after transplantation revealed that fibrosis of myocardium and vascular stenotic lesions, which are pathological conditions characteristic of the chronic rejection reaction, were significantly suppressed in the MR16-1-treated group as compared to the control group. Thus, MR16-1 administration was demonstrated to have the effect of suppressing chronic rejection reaction. Specifically, the present inventors discovered for the first time that the rejection reaction in the chronic phase after organ transplantation was suppressed by administering an anti-IL-6 receptor antibody.

The present invention concerns the use of oxygen antagonists for inducing stasis in cells, tissues, and / or organs in vivo or in an organism overall. It includes methods and apparatuses for achieving stasis in any of these biological materials, so as to preserve and / or protect them. In specific embodiments, therapeutic methods and apparatuses for organ transplantation, hyperthermia, wound healing, hemorrhagic shock, cardioplegia for bypass surgery, neurodegeneration, hypothermia, and cancer is provided.

The present invention provides devices and methods for modulating or blocking renal sympathetic nerve activity by applying laser energy to the renal artery wall to effect ablation of the renal nerve or nerves. The devices and methods of the invention may be useful in the treatment of cardiovascular and renal disease resulting from hypertension. In addition the devices and methods of the invention may be useful for reducing reflex hypertension following cyclosporine administration after organ transplantation.

The present invention concerns the use of oxygen antagonists and other active compounds for inducing stasis or pre-stasis in cells, tissues, and / or organs in vivo or in an organism overall, in addition to enhancing their survivability. It includes compositions, methods, articles of manufacture and apparatuses for enhancing survivability and for achieving stasis or pre-stasis in any of these biological materials, so as to preserve and / or protect them. In specific embodiments, there are also therapeutic methods and apparatuses for organ transplantation, hyperthermia, wound healing, hemorrhagic shock, cardioplegia for bypass surgery, neurodegeneration, hypothermia, and cancer using the active compounds described.

The present invention relates to 5-thia-omega-substituted phenylprostaglandin E derivatives of the formula (I)(wherein, all the symbols are as defined in the specification), process for producing them and pharmaceutical compositions comprising them as active ingredient.The compounds of the formula (I) can bind to PGE2 receptors (especially, subtype EP4) strongly, so they are expected to be useful for prevention and / or treatment of immunological diseases (autoimmune diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, Sjoegren's syndrome, chronic rheumarthrosis and systemic lupus erythematosus etc., and rejection after organ transplantation etc.), asthma, abnormal bone formation, neuronal cell death, lung failure, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardiac ischemia, systemic inflammatory response syndrome, ambustion pain, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, and shock etc. Further, it is thought that EP4 subtype receptor relates to sleeping disorder and blood platelet aggregation, so the compounds of the present invention are expected to be useful for the prevention and / or treatment of such diseases.

The invention relates to a two-layer cell culture system organ chip and a preparation method thereof. The organ chip comprises a two-layer cell culture system, wherein each layer comprises a culture solution micro-fluid channel, a medicament micro-fluid channel, cell culture chambers and a medicament testing tank; a micro structure and micro-fluid channels are designed on the organ chip, two cells are respectively fixed on each specific cell culture chamber, and intercellular signal transmission and interaction between the cells are performed by virtue of the micro-fluid channels. The organ chip realizes the parallel implantation and co-culture of two or more cells, is simple in operation, reduces the dose of practical samples, simplifies the cell implantation process, has the characteristics of portability, economic performance, high efficiency and accuracy, and can be used for independently performing cell seeding and culture and detection of medicament toxicity or pharmacological activity. The two-layer cell culture system organ chip is a novel organ chip with miniaturization, automation and visualization, prepared by simulating the structures and functions of a human organ, and can be used for providing the effective theoretical basis for tissue and regeneration engineering, organ transplantation and medicament evaluation.

The present invention provides compositions and methods of treatment of HCV infected subjects that are not sensitive to interferon treatment. Further, compositions and methods are provided for prevention of organ transplant rejection. The compositions of the invention comprise an anti microRNA-122 oligonucleotide, and are made for administration to a primate.

The present invention is directed to systems and methods for assessing the success of the transplant of a cell, tissue, or organ before and after transplant. Protein array technology is used to obtain a biomarker pattern for the cell, tissue, or organ that is being considered for transplant or that has been transplanted. Samples for the identification of biomarkers and biomarker patterns are obtained from the cell, tissue or organ itself, or from a body fluid of the donor or recipient. Sample biomarker data are compared to reference biomarker data obtained from donors, recipients or cells, tissues or organs that have been transplanted. Correlation of a sample biomarker pattern with the reference biomarker pattern, where transplant outcome for the samples used for the reference biomarkers is known, permits a suggested treatment determination. A computerized system to identify the condition of transplant before or after implantation is also provided.

Methods and compositions including combined use of a serine protease inhibitor and adenosine when administered as a single pharmaceutical composition, concomitantly or sequentially in any order to a living subject for preventing organ ischemia or reperfusion injury. The methods and compositions disclosed herein can be used in such procedures as cardiac surgery, non-surgical cardiac revascularization, organ transplantation, perfusion, ischemia, reperfusion, ischemia-reperfusion injury, oxidant injury, cytokine induced injury, shock induced injury, resuscitations injury or apoptosis.

A compound of the formula (I):wherein R is hydrogen or C2-6 alkanoyl; X is halogen; and ring A is benzene ring which is optionally substituted by 1 to 4 substituents selected from {circle around (1)} halogen, {circle around (2)} hydroxy, {circle around (3)} C1-6 alkoxy optionally substituted by halogen or phenyl, {circle around (4)} C1-6 alkylthio optionally substituted by halogen or phenyl, {circle around (5)} C1-6 alkyl optionally substituted by halogen, {circle around (6)} C2-6 alkanoylamino or {circle around (7)} carboxy optionally esterified by C1-6 alkyl, or a salt thereof; which can be used for preventing or treating inflammatory disease, arthritis, chronic rheumatoid arthritis, autoimmune diseases, or rejection after organ transplantation.

Methods and compositions are described for the treatment of type I insulin-dependent diabetes mellitus and other conditions using newly identified stem cells that are capable of differentiation into a variety of pancreatic islet cells, including insulin-producing beta cells, as well as hepatocytes. Nestin has been identified as a molecular marker for pancreatic stem cells, while cytokeratin-19 serves as a marker for a distinct class of islet ductal cells. Methods are described whereby nestin-positive stem cells can be isolated from pancreatic islets and cultured to obtain further stem cells or pseudo-islet like structures. Methods for ex vivo differentiation of the pancreatic stem cells are disclosed. Methods are described whereby pancreatic stem cells can be isolated, expanded, and transplanted into a patient in need thereof, either allogeneically, isogeneically or xenogenically, to provide replacement for lost or damaged insulin-secreting cells or other cells.

Compositions and methods are provided for culturing in vitro potentially regenerative cells (PRCs) from which functional tissue-organs are regenerated. In one aspect of the invention, a tissue culture medium is provided which comprises at least 50% of water and a sterol compound that is dissolved in a fatty acid-containing oil at a concentration at least 0.1% by weight based on the weight of the oil and added to the water. The culture medium can be used to culture PRCs that are isolated from the body of a mammal to generate functional tissue-organs in vitro with substantially the same physiological structure and function as the corresponding ones existing in vivo and in situ. The cultured PRCs, tissues, and tissue-organs can serve as valuable models for scientific investigation in life sciences, nutraceutical discovery, drug screening, pharmacokinetic studies, medical devices and tissue / organ transplantation.

Medical devices with novel spark gap electrode designs, able to control manually or automatically the electrodes gap are provided. These devices are used to generate a shock wave created by the rapid expansion and collapse of a plasma bubble that is formed between two spark gap electrodes placed in a special liquid medium, when a high differential voltage (kV) is applied to the electrodes. The resulting shock wave impacts a reflector to direct the energy into the body of an animal or a human toward the desired treatment location. This electro-hydraulic principle to create acoustic shock waves as a method of treatment is in use in the medical (lithotripsy, orthopedic use, wound treatment, burns, post-operative treatment, pain treatment, diagnosis, skin and organ transplantation supporting devices, arteriosclerosis treatment), cosmetic (treatment of scars and cellulite) and veterinary (treatment of musculoskeletal disorders) fields.

The present invention provides methods of characterizing organ transplant rejection or inflammatory conditions associated with organ transplant rejection using gene expression profiling.

Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage.

The present invention concerns the use of oxygen antagonists for inducing stasis in cells, tissues, and / or organs in vivo or in an organism overall. It includes methods and apparatuses for achieving stasis in any of these biological materials, so as to preserve and / or protect them. In specific embodiments, therapeutic methods and apparatuses for organ transplantation, hyperthermia, wound healing, hemorrhagic shock, cardioplegia for bypass surgery, neurodegeneration, hypothermia, and cancer is provided.

The invention relates to a method for amplifying cells, in particular to an in vitro amplification adjustable T cell method, belonging to the technical field of biomedical science. The invention uses Rapamycin combined with TGF-beta to induce human T cell in vitro to become adjustable T cell having immune suppression function, having the following advantages in : 1. enough quantity; and 2. capability of resisting differentiation towards Th 17 cell. The invention overcomes plural defects of natural adjustable T cell, and has larger curing advantages in curing inflammation diseases, autoimmune diseases and prevention of immunity rejection of organ implantation.

The present invention provides an isolated population of adult hematopoietic stem cells (HSC) derived from embryonic stem cells (ESC) induced to differentiate in vitro by culturing ESCs in a medium with stem cell factor, interleukin (IL)-3, and IL-6. HSC of immunophenotype c-kit+ or c-kit+ / CD45+ from this population are isolated and injected either intra bone marrow or intravenously into myeloablated recipient individuals. This method allows for the establishment of banks of allogeneic ESC-derived adult stem cells for treatments of autoimmune diseases, immune deficiencies and induction of immunotolerance during organ transplantation. These allogeneic ESC-derived adult hematopoietic stem cells (HSC) may be used in reconstituting bone marrow, without the development of teratomas or graft versus host disease, despite crossing histocompatibility barriers. Additionally, allogeneic ESC-derived HSC can be used to prevent the development of autoimmune diseases or organ rejection during transplantation.

The present invention relates to a cyclosporin analog of the following formula (I) or a pro-drug or pharmaceutically acceptable salt thereof:whereinA is of the formula:where Q, W, X, Y, and Z are defined herein. In a second embodiment, the present invention relates to pharmaceutical compositions comprising pro-drugs or pharmaceutically acceptable salts of the compounds of the present invention and the use thereof for treating autoimmune diseases or for the prevention of organ transplantation rejection in a subject. In a third embodiment, the present invention relates to processes for the production of novel cyclosporin analogs of the present invention.

The invention provides a process for preparing rapamycin by using a microbial fermentation method. The method comprises the following steps of: culturing streptomyces hygroscopicus of which the collection number is CGMCC No.5145 in a slant culture medium, and inoculating into a fresh seed culture medium for culturing; and inoculating 2 percent of strain cultured by using the seed culture medium into a fresh fermentation culture medium for fermenting and culturing to obtain a fermentation liquor containing rapamycin, and separating and purifying the fermentation liquor containing the rapamycinaccording to the solubility difference of the rapamycin in water and an organic solvent. In a method provided by the invention, a production technology for producing high-purity rapamycin at low costis provided. By reducing the cost of a raw material, an immunosuppressive medicament which is economically acceptable, safe and effective can be provided for an organ transplantation patient. The product purity of the rapamycin prepared with the process is over 95 percent, and the recrystallization yield is over 84 percent.

Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Two examples of such recombinant APC mutants are KKK191-193AAA-APC and RR229 / 230M-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis. At risk patients include, for example, those suffering (severe) sepsis, ischemia / reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative diseases, or those undergoing organ transplantation or chemotherapy, among other conditions. Methods of screening for variants of recombinant protein C or APC that are useful in accordance with the invention are also provided.

The present invention encompasses a liquid bioartificial tissue for restoring tissue and organ function to an injured or damaged organ in a human subject. The liquid bioartificial tissue is injected into a target organ and can significantly restore organ function within two weeks. The invention also encompasses a cell culture medium comprising ascorbic acid (or other free-radical scavengers and / or anti-oxidants) that is used for pre-treating transplantable cells prior to organ transplantation. Pre-treatment with ascorbic acid increases transplanted cell viability and colonization by nearly fifty-fold compared with untreated cells. The invention is particularly useful for treating ischemic heart damage following myocardial infarction.

Subject of the present invention is a biomarker for graft failure and / or mortality after organ transplantation. Procalcitonin was found to be a useful marker for the prediction or risk stratification for graft failure and / or mortality of a subject who has received an organ transplant and monitoring and therapy guidance of such subject.

The invention relates to an SNPs detection method, and concretely relates to a method for detecting specifically amplified products through a one-step PCR reaction and a nucleic acid detection test paper strip in a same reaction system. The method comprises the following steps: nonspecifically amplifying fragments containing SNPs sites through first PCR temperature cycling; specifically amplifying bases containing the SNPs sites through AS-PCR (allele specific polymerase chain reaction); and detecting the specifically amplified products by the nucleic acid detection test paper strip. The method can also be used for detecting mononucleotide mutation. The method which has the characteristics of high sensitivity, strong specificity, simple operation, short time, and rapid and reliable detection result combines respective advantages of proteins and nucleic acids. The invention also relates to applications of a kit in the detection of known drug-resistant gene of pathogens, the mating selection of a donor and an acceptor in organ transplantation, and the discrimination of the identity of a criminal or paternity tests in forensic researches.

The invention relates to a preparation method of an animal and human primitive pluripotent stem cell, a kit and use thereof. The preparation method of the animal and human primitive pluripotent stem cell provided by the invention includes letting an animal and human primitive ectoderm-like pluripotent stem cell contact at least one MAPK pathway inhibiting factor, at least one WNT signaling pathway regulatory factor, at least one LIF / STAT3 pathway regulatory factor and at least one FGF pathway regulatory factor so as to generate the animal and human primitive pluripotent stem cell. The invention also relates to a composition, medium or kit for preparation of the animal and human primitive pluripotent stem cell, as well as the primitive pluripotent stem cell prepared thereby and its use. The primitive pluripotent stem cell involved in the invention can be used for preparation of the chimeras of different animal and human species and the like, and is expected to be used for disease model establishment, drug testing and organ transplantation, etc.

A method for the early diagnosis of breast, lung, pancreatic and colon growths and cancers as well as conditions associated with donor and recipient organ transplants, both before and after transplantation to identify and allow treatment of possible transplanted organ rejection and other disease conditions related and unrelated to the transplantation, compares the gene expression patterns from a patient's peripheral blood monocytes-lymphocyte's gene system with either the similar gene expression patterns of a normal person, or with the similar gene expression patterns of a person known to have the condition being screened for. Differences between the patient's gene expression patterns for particular genes and the normal patterns indicates the presence of the condition with the number of differences indicating the probability of the condition. Similarities between the patient's gene expression patterns for those particular genes and the patterns of a person known to have the condition indicates the presence of the condition with the number of similarities indicating the probability of the condition. Portions of the method may be performed with the use of a microfluidic machine.