Intramyocardial injection of autologous bone marrow

Inactive Publication Date: 2004-08-19
KOMOWSKI RAN +3
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  • Abstract
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  • Application Information

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Benefits of technology

0025] Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Granulocyte-Colony Stimulatory Factor (G-CSF) are stimulatory cytokines for monocyte maturation and are multipotent hematopoietic growth factors, which are utilized in clinical practice for various hematological pathologies such as depressed white blood cell count (i.e., leukopenia or granulocytopenia or monocytopenia) which occurs usually in response to immunosuppressive or chemotherapy treatment in cancer patients. GM-CSF has also been described as a multilineage growth factor that induces in vitro colony formation from erythroid burst-forming units, eosinophil colony-forming units (CSF), and multipotential (CSF), as well as from granulocyte-macrophage CSF and granulocyte CFU. (Bot F. J., Exp Hematol 1989, 17:292-5). Ex-vivo exposure to GM-CSF has been shown to induce rapid proliferation of CD-34+ progenitor cells (Egeland T. et al., Blood 1991; 7

Problems solved by technology

However, it is believed that complex interactions among several growth factor systems a

Method used

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  • Intramyocardial injection of autologous bone marrow
  • Intramyocardial injection of autologous bone marrow

Examples

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example 1

[0027] Effect of Bone Marrow Cultured Media on Endothelial Cell Proliferation

[0028] Studies were conducted to determine whether aspirated pig autologous bone marrow cells obtained secreted VEGF, a potent angiogenic factor, and MCP-1, which recently has been identified as an important angiogenic co-factor. Bone marrow was cultured in vitro for four weeks. The conditioned medium was added to cultured pig aortic endothelial cells (PAECs), and after four days proliferation was assessed. VEGF and MCP-1 levels in the conditioned medium were assayed using ELISA. During the four weeks in culture, BM cells secreted VEGF and MCP-1, such that their concentrations increased in a time-related manner. The resulting conditioned medium enhanced, in a dose-related manner, the proliferation of PAECs. The results indicate that BM cells are capable of secreting potent angiogenic cytokines such as VEGF and MCP-1 and of inducing proliferation of vascular endothelial cells.

[0029] Pig Bone Marrow Culture

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example 2

[0045] Effects of Hypoxia on VEGF Secretion by Cultured Pig Bone Marrow Cells

[0046] It was demonstrated that hypoxia markedly increases the expression of VEGF by cultured bone marrow endothelial cells, results indicating that ex-vivo exposure to hypoxia, by increasing expression of hypoxia-inducible angiogenic factors, can further increase the collateral enhancing effect of bone marrow cells and its conditioned media to be injected in ischemic muscular tissue. Pig bone marrow was harvested and filtered sequentially using 300.mu. and 200.mu. stainless steel mesh filters. BMCs were then isolated by Ficoll-Hypaque gradient centrifugation and cultured at 33.degree. C. with 5% CO2 in T-75 culture flasks. When cells became confluent at about 7 days, they were split 1:3 by trypsinization. After 4 wks of culture, the BMCs were either exposed to hypoxic conditions placed in a chamber containing 1% oxygen) for 24 to 120 hrs, or maintained under normal conditions. The resulting conditioned med...

example 3

[0048] Effect of Bone Marrow Cultured Media on Endothelial Cell Tube Formation

[0049] It was demonstrated, using pig endothelial cells and vascular smooth muscle cells co-culture technique, that the conditioned medium of bone marrow cells induced the formation of structural vascular tubes in vitro. No such effect on vascular tube formation was observed without exposure to bone marrow conditioned medium. The results suggest that bone marrow cells and their secreted factors exert pro-angiogenic effects.

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Abstract

A method of treating cardiac or myocardial conditions comprises the administration of an effective amount of autologous bone marrow. The bone marrow may optionally be stimulated and/or administered in combination with a pharmaceutical drug, protein, gene or other factor or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation or migration or blood vessel formation.

Description

[0001] This application is directed to a method of injecting autologous bone marrow. More specifically, this invention is directed to intramyocardial injection of autologous bone marrow to enhance collateral blood vessel formation and tissue perfusion.[0002] The use of recombinant genes or growth-factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Kornowski, R., et al., "Delivery strategies for therapeutic myocardial angiogenesis", Circulation 2000; 101:454-458. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Unger, E. F., et al., "Basic fibroblast growth factor enhances myocardial collateral flow in a canine model", Am J Physiol 1994; 266:H1588-1595; Banai, S. et al., "Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs", Circulation 1994; 83-2189; Lazarous, D. F...

Claims

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Application Information

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IPC IPC(8): A61K35/28A61K38/17A61K38/19
CPCA61K35/28A61K38/1709A61K38/193A61K2300/00
Inventor KOMOWSKI, RANFUCHS, SHMUELEPSTEIN, STEPHEN E.LEON, MARTIN B.
Owner KOMOWSKI RAN
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