36 results about "Endothelial Precursor Cell" patented technology

Described are methods of modulating stem / progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem / progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

Described are methods of modulating stem / progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem / progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

Methods and compositions based on the elucidation of the role of Prox1 in lymphatic tissue development in normal and tumor tissue are provided. Included are methods for determining the extent of lymphatic involvement in a tumor, methods for purifying endothelial precursor cells predisposed to develop into lymphatic tissue, and methods for promoting the development of lymphatic tissue. Pharmaceutical compositions and gene therapy vectors useful in the latter methods are provided.

In vitro methods are disclosed that rely on a novel phenomenon of secondary sprouting by cultured endothelial precursor cells, after angiogenic-like tube formation and collapse have occurred on a basement membrane matrix. Particularly disclosed is an in vitro method of isolating and expanding, from a mixed population of mammalian cells originating from a tissue sample, a cellular population enriched for endothelial sprout cells, including cells having one or more physiological and / or immunological features of endothelial precursor cells. Also disclosed is an in vitro method for a screening a substance for potential proangiogenic or antiangiogenic activity.

A method for regenerating a blood vessel comprising introducing a cell-containing fluid containing vascular endothelial precursor cells and cells to be removed into a cell separator which allows at least the cells to be removed to substantially pass through but substantially captures the vascular endothelial precursor cells; recovering the vascular endothelial precursor cells once captured on said cell separator by introducing a fluid into the said cell separator; and using the recovered vascular endothelial precursor cells for regenerating a blood vessel.

Disclosed are compositions and methods for preventing, treating, or reducing symptoms associated with a myocardial or related disorder such as an infarction. In one embodiment, the method includes administering a therapeutically effective amount of a nucleic acid encoding at least one morphogen; or an effective fragment thereof. Preferred morphogens include the human Sonic Hedghog (Shh), human Desert Hedgehog (Dhh), and human Indian Hedgehog (Ihh) proteins. The methods can be used alone or in combination with other methods involving administration of an angiogenic protein, hematopoietic protein, or endothelial precursor cells (EPCs).

Disclosed are compositions and methods for promoting or accelerating wound healing and preventing, treating, or reducing symptoms associated with wounds or wounding disorders such as diabetic ulcers and burns. In one embodiment, the method includes administering a therapeutically effective amount of a nucleic acid encoding at least one morphogen, or an effective fragment thereof. Preferred morphogens include the human Sonic Hedghog (Shh), human Desert Hedgehog (Dhh), and human Indian Hedgehog (Ihh) proteins. The methods can be used alone or in combination with other methods involving administration of an angiogenic protein, a hematopoietic protein, or cells such as endothelial cells or endothelial precursor cells.

In vitro methods are disclosed that rely on a novel phenomenon of secondary sprouting by cultured endothelial precursor cells, after angiogenic-like tube formation and collapse have occurred on a basement membrane matrix. Particularly disclosed is an in vitro method of isolating and expanding, from a mixed population of mammalian cells originating from a tissue sample, a cellular population enriched for endothelial sprout cells, including cells having one or more physiological and / or immunological features of endothelial precursor cells. Also disclosed is an in vitro method for a screening a substance for potential proangiogenic or antiangiogenic activity.

The present invention provides a method for subculturing primate embryonic stem cells, and a method for inducing differentiation of the same cell into a vascular endothelial cell and a blood cell. The present invention provides a method comprising culturing primate embryonic stem cells in a medium containing a protein component without using feeder cells and cytokines in a container coated with an extracellular matrix, detaching colonies of the resulting embryonic stem cells in the presence of a cytodetachment agent, and plating the colonies in the similar medium, and a method comprising culturing primate embryonic stem cells in a serum-containing or not containing medium in the presence of cytokine, adhesion-culturing the resulting embryoid body or embroyid body-analogous cellular aggregate in the presence of a cytokine to obtain specific precursor cells, and separating non-adherent cells and adherent cells from the specific precursor cells to obtain blood cells and vascular endothelial precursor cells.

Compositions and processes for promoting wound healing are provided by the present invention which increase the rate and completeness of wound healing. Broadly described, an inventive composition includes a degradable scaffold of biocompatible material and a cell involved in wound healing, or a predecessor of such a cell, disposed in contact with the scaffold. In one embodiment, an albumin scaffold is provided with an endothelial cell predecessor disposed therein. Optionally, a cell involved in wound healing or a predecessor of such a cell is administered by local or systemic injection in conjunction with application of an inventive composition. Processes for promoting wound healing are provided as well as processes for producing the described compositions for promoting healing.

The present invention provides methods for producing hematopoietic stem cells or vascular endothelial precursor cells, wherein the methods comprise the step of separating PCLP1-positive cells from the hematopoietic tissues of an individual, and then culturing the obtained cells. PCLP1-positive cells obtained from the hematopoietic tissues of an individual can be cultured for a long time, and during culture they produce large quantities of hematopoietic stem cells or vascular endothelial precursor cells. The hematopoietic stem cells or vascular endothelial precursor cells obtainable by the present invention can be utilized for regenerative medicine.

The present invention provides a prophylactic / therapeutic agent for Alzheimer's disease comprising a substance that inhibits the action of β-amyloid 1-40 to suppress vascular endothelial precursor cell differentiation and / or endothelial precursor differentiation from stem cells and / or a substance that promotes vascularization as an active ingredient. The present invention also provides a screening method for a substance that inhibits the action of β-amyloid 1-40 to suppress vascular endothelial precursor cell differentiation and / or endothelial precursor differentiation from stem cells and / or a substance that promotes vascularization.

The invention relates to a culture medium and a method for inducing pluripotent stem cells to differentiate into hematopoietic precursor cells. Specifically, the method comprises the following steps: 1) preparing hematopoietic endothelial precursor cells by a method of differentiating human pluripotent stem cells to generate the hematopoietic endothelial precursor cells; and 2) preparing the hematopoietic precursor cells by a method for promoting the hematopoietic endothelial precursor cells to differentiate into the hematopoietic precursor cells. In the preparation process, the culture medium is adopted, a random rotation mode is adopted for culture, the excellent effective efficiency is obtained, and components of the culture medium are definite.

AC133+ / CD34+ cells isolated from human bone marrow can be stimulated with the pro-angiogenic factors VEGF, bFGF, and heparin, resulting in the generation of a population of cells that is adherent and possesses many of the same properties as mature endothelial cell types, HMVECs and HUVECs. The newly-formed, endothelial-like cells are referred as adherent endothelial precursor cells (aEPCs); these cells appear to be intermediates between haematopoietic stem cells (HSCs) and mature endothelial cells. Direct comparison of aEPCs with HMVECs and HUVECs in several in vitro functional assays, such as tube formation, migration, invasion, and expression of cells surface markers, reveals differences and similarities. In a Matrigel™ matrix angiogenesis assay the aEPCs form vessels in vivo and interact with human ovarian cancer cells. Mouse cell lines that are useful models for tumor endothelial cells are identified by determining mRNA and protein expression levels of murine homologs of tumor endothelial markers. Mouse cell lines selected as models for tumor endothelial cells can be used to evaluate pro-angiogenic and anti-angiogenic factors.

The present invention relates to a bispecific fusion protein, comprising (a) a first polypeptide which binds to collagen, and (b) a second polypeptide which binds to endothelial precursor cells. Also, pharmaceutical compositions are disclosed, comprising the fusion protein of the invention, as well as methods for using the fusion protein, in particular for treating or preventing lesions of vessels and tissues.

Disclosed herein are tissue scaffold materials with microspheres of one density embedded in hydrogel of a different density. The disclosed materials have improved ability to facilitate cellular invasion and vascularization for wound healing and tissue regeneration. The inventors have found that materials having components with different densities promotes invasion of cells, including desirable cells such as fibroblasts and endothelial precursor cells, into the scaffold.

The invention relates to the use of erythropoietin for stimulation of the physiological mobilisation, proliferation and differentiation of endothelial precursor cells, for stimulation of vasculogenesis, for the treatment of diseases related to a dysfunction of endothelial precursor cells and for the production of pharmaceutical compositions for the treatment of such diseases and pharmaceutical compositions comprising erythropoietin and other agents suitable for stimulation of endothelial precursor cells.

The invention relates to the use of erythropoietin for stimulation of the physiological mobilisation, proliferation and differentiation of endothelial precursor cells, for stimulation of vasculogenesis, for the treatment of diseases related to a dysfunction of endothelial precursor cells and for the production of pharmaceutical compositions for the treatment of such diseases and pharmaceutical compositions comprising erythropoietin and other agents suitable for stimulation of endothelial precursor cells.

The invention relates to a method for obtaining endothelial cells from human pluripotent stem cells by efficient differentiation. The method comprises following steps: step 1, the human pluripotent stem cells are cultured in a culture medium containing Actin A, BMP4 and Y27632 for 3 days, and are differentiated into mesoderm endothelial precursor cells; and step 2, the culture medium is changed into a culture medium containing FGF2, VEGF, BMP4 and SB431542 on the fourth day, the human pluripotent stem cells are cultured for 4 days, and endothelial progenitor cells are obtained.

The invention provides a use of CD133<+> endothelial precursor cells, and concretely relates to a use of the CD133<+> endothelial precursor cells in the preparation of medicinal compositions for treating diabetic foot. The specific endothelial precursor cells can substantially improve the symptoms of diabetic foot patients in a specific intra-arterial application mode, and even reverse serious diabetic foot patients in order to provide a new clinic application for the treatment of the diabetic foot. The CD133<+> endothelial precursor cells are autologous, are used in autograft, have no ethical defects, and are safe and feasible.

A treatment method capable of regenerating new blood vessels at an affected site of a peripheral blood vessel that is highly safe with respect to the human body and is easily performed. More specifically, a vascularization therapy that increases the number of newly formed blood vessels of an affected site by immersing in carbonated warm water having a carbon dioxide concentration of 700 ppm or more and a water temperature of 33 to 42° C. A vascularization therapy that increases the number of vascular endothelial cells in tissue of an affected site by 1.5 times or more and that increases the number of endothelial precursor cells in the peripheral blood at an affected site by 1.1 times or more by immersing the affected site of a peripheral blood vessel in the aforementioned carbonated warm water.

The invention provides preserving fluid for long-term preservation of endothelial precursor cell for over-expressing VEGF. The preserving fluid comprises the following components: albumin, glucose, glycol, dimethyl sulfoxide, epidermal growth factor, magnesium sulfate, L-glutamine and betamethasone. The invention further provides an application method of the preserving fluid. Through the application method, the endothelial precursor cell for over-expressing VEGF is preserved with the preserving fluid, the endothelial precursor cell for over-expressing VEGF can be preserved for a long time, andresuscitated cell can properly maintain a proliferation function and biological characteristics of the endothelial precursor cell.

An isolated peptide useful as a selective antagonist of mammalian R-cadherin comprises 3 to 30 amino acid residues, three contiguous residues of the peptide having the amino acid sequence Ile-Xaa-Ser; wherein Xaa is an amino acid residue selected from the group consisting of Asp, Asn, Glu, and Gln. Preferably Xaa is Asp or Asn. In one preferred embodiment the peptide is a cyclic peptide having 3 to 10 amino acid residues arranged in a ring. The selective R-cadherin antagonist peptides of the invention are useful for inhibiting the targeting of stem cells, such as endothelial precursor cells, to developing vasculature, for inhibiting R-cadherin mediated cellular adhesion, and for inhibiting retinal angiogenesis.

The invention relates to a bispecific construct comprising a first polypeptide that binds to collagen and a second polypeptide which binds to endothelial precursor cells. The invention further relatesto the use of said fusion protein for producing a pharmaceutical composition used for treating vascular and / or tissue lesions.

The invention discloses the method for separating vessel esoderma fore-body cell from bone marrow and extracorporal culturing. The method comprises the following steps: 1 getting marrow cell; 2 collecting individual cell; 3 making EBM-2 cell culture liquid; 4 cell culturing; 5 passage culturing. The bFGF and VEGF are added in EBM-2 cell culture liquid to improve proliferation of vessel esoderma fore-body cell. So the invention can get many vessel esoderma fore-body cells in a short time.

The present invention provides a composition for stimulating the mobilization of endothelial precursor cells, which comprises substance-P (SP). Substance-P according to the invention exhibits an activity of stimulating the mobilization of endothelial precursor cells from the bone marrow, thereby stimulating vasculogenesis. Thus, substance-P exhibits excellent effects on the prevention or treatment of diseases, including myocardial infarction, angina, ischemic stroke, cerebrovascular dementia, cerebral infarction, sequelae of cerebral injury, spinal cord injury, sequelae of spinal nerve injury, degenerative diseases, sequelae of cerebral infarction, peripheral nerve disorders, presbyopia, degenerative hearing loss, sequelae of brain surgery, and diabetic ulcer, which are accompanied by ischemic vascular injury or traumatic vascular injury.

An isolated peptide useful as a selective antagonist of mammalian R-cadherin comprises 3 to 30 amino acid residues, three contiguous residues of the peptide having the amino acid sequence Ile-Xaa-Ser; wherein Xaa is an amino acid residue selected from the group consisting of Asp, Asn, Glu, and Gln. Preferably Xaa is Asp or Asn. In one preferred embodiment the peptide is a cyclic peptide having 3 to 10 amino acid residues arranged in a ring. The selective R-cadherin antagonist peptides of the invention are useful for inhibiting the targeting of stem cells, such as endothelial precursor cells, to developing vasculature, for inhibiting R-cadherin mediated cellular adhesion, and for inhibiting retinal angiogenesis.

The invention relates to the use of low-dose erythropoietin for stimulating physical mobilization, proliferation, and differentiation of endothelial precursor cells, stimulating vasculogenesis, treating diseases that are linked to a dysfunction of endothelial precursor cells, and producing pharmaceutical compositions used for the treatment of such diseases as well as pharmaceutical compositions containing erythropoietin and other appropriate agents for stimulating endothelial precursor cells.