Injection of bone marrow-derived cells and medium for angiogenesis

A myeloid cell, angiogenesis technique with applications in enhancing collateral vessel formation) and tissue perfusion. ,Intramyocardial injection of autologous bone marrow and transfected bone marrow cells can solve problems such as gaps

Inactive Publication Date: 2006-09-27
MYOCARDIAL THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although therapeutic angiogenesis as a new form holds great promise for the treatment of patients with coronary artery disease, there is conside

Method used

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  • Injection of bone marrow-derived cells and medium for angiogenesis
  • Injection of bone marrow-derived cells and medium for angiogenesis
  • Injection of bone marrow-derived cells and medium for angiogenesis

Examples

Experimental program
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Effect test

Embodiment 1

Effects of Bone Marrow Culture Medium on the Proliferation of Endothelial Cells

[0064] A study was performed to determine whether the obtained aspirated porcine autologous bone marrow cells secreted VEGF, a potent angiogenic factor, and MCP-1, which was recently identified as an important angiogenic cofactor. Bone marrow was cultured in vitro for four weeks. Conditioned medium was added to cultured porcine aortic endothelial cells (PAECs), and proliferation was assessed four days later. Conditioned media were analyzed for VEGF and MCP-1 levels by ELISA. During four weeks of culture, BM cells secreted VEGF and MCP-1 such that their concentrations increased in a time-dependent manner. The resulting medium enhanced the proliferation of PAECs in a dose-related manner. The results suggest that BM cells can secrete potent angiogenic factors such as VEGF and MCP-1, and can induce proliferation of vascular endothelial cells.

porcine bone marrow culture

[0065] Bone marrow (BM)...

Embodiment 2

Effect of Hypoxia on Secretion of VEGF by Cultured Porcine Bone Marrow Cells

[0074] It was confirmed that hypoxia significantly increases the expression of VEGF in cultured bone marrow endothelial cells, and the results suggest that exposure to hypoxia in vitro can further increase the expression of hypoxia-induced angiogenic factors, which can further increase the expression of bone marrow to be injected in ischemic muscle tissue. Collateral enhancement effects of cells and their conditioned media. Porcine bone marrow was harvested and successively filtered through 300μ and 200μ stainless steel mesh filters. BMCs were then isolated by Ficoll-Hypaque gradient centrifugation and cultured at 33 °C with CO in T-75 culture flasks 2 is 5%. When the cells became confluent at approximately 7 days, they were trypsinized 1:3 to separate. After 4 weeks in culture, BMCs were either exposed to hypoxic conditions (placed in a chamber containing 1% oxygen) for 24 to 120 hours,...

Embodiment 3

[0076] demonstrated that the conditioned medium of bone marrow cells induces the formation of structural vascular tubes in vitro using a co-culture technique of porcine endothelial cells and vascular smooth muscle cells. This effect on vascular tube formation was not observed in the absence of exposure to bone marrow-conditioned media. The results suggest that myeloid cells and the factors they secrete exert pro-angiogenic effects.

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Abstract

Methods are provided for enhancing capacity of impaired bone marrow cells to promote angiogenesis when introduced into an ischemic site in a patient by transfecting early attaching cells derived from bone marrow in culture with an angiogenesis promoting transgene. Methods are also provided for utilizing such early attaching cells derived from autologous bone marrow, or media derived from these cells while the cells are grown in culture (which need not be from autologous cells) to deliver angiogenesis-promoting transgenes or proteins to a patient. The transfected early attaching cells, or media derived from these cells while the cells are grown in culture, are introduced into an ischemic tissue, such as the heart, to enhance formation of collateral blood vessels. The cells or media can also be injected into the blood stream (artery supplying the ischemic tissue, or any other artery or vein).

Description

[0001] related application [0001] This application claims priority to U.S. Application Serial No. 10 / 618,183, filed July 10, 2003, which is a continuation-in-part of U.S. Patent Serial No. 10 / 160,514, filed June 6, 2002, which is Continuation-in-Part of U.S. Patent Serial No. 09 / 868,411, filed June 14, 2001, a national phase application of International Application No. PCT / US00 / 08353, filed March 30, 2000, the national phase This application benefits from US Provisional Patent Application Serial No. 60 / 138,379, filed June 9, 1999, and US Provisional Patent Application Serial No. 60 / 126,800, filed March 30, 1999. technical field [0002] This application relates to methods of injecting autologous bone marrow and bone marrow cells. More specifically, the present invention relates to intramyocardial injection of autologous bone marrow and transfected bone marrow cells, and / or media derived from these cells when grown in culture (...

Claims

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Application Information

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IPC IPC(8): A61K35/00A61K38/43A61K45/00A01N1/00A01N61/00A01N43/04C12N5/00A61K35/12A61K48/00C07K14/47C07K14/52C07K14/535C12NC12N5/071
CPCA61K2035/124C07K14/523C12N2502/1358C07K14/4702C07K14/535A61K48/00C12N2799/022C12N5/0691A61P21/00A61P3/06A61P43/00A61P7/04A61P9/00A61P9/04A61P9/06A61P9/10A61P9/14
Inventor S·爱泼斯坦S·富赫斯R·科尔诺维斯基M·B·列昂K·W·卡彭特
Owner MYOCARDIAL THERAPEUTICS INC
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