Methods of using regenerative cells in the treatment of peripheral vascular disease and related disorders

a technology of peripheral vascular disease and regenerative cells, applied in the field of adipose-derived regenerative cells, can solve the problems of tissue ischemia, aberrant blood flow, occlusion of the vessel, etc., and achieve the effect of promoting differentiation

Inactive Publication Date: 2012-03-08
LOREM VASCULAR PTE LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The system enables the rapid production of high-yield, pure regenerative cells that can be administered directly to patients, improving angiogenesis and tissue survival, thereby effectively treating peripheral vascular disease with increased efficiency and reduced costs.

Problems solved by technology

This can lead to occlusion of the vessel, aberrant blood flow, and ultimately to tissue ischemia.
For example, narrowing of the artery that supplies blood to the intestine (i.e., the superior mesenteric artery) can result in severe postprandial pain in the lower abdomen resulting from the inability of the occluded vessel to meet the increased oxygen demand arising from digestive and absorptive processes.
Similarly, PAD in the leg can lead to intermittent pain, usually in the calf, that comes and goes with activity.
However, many patients have a form of disease that is not anatomically suitable for surgical intervention.
Peripheral vascular disease is also manifested in atherosclerotic stenosis of the renal artery, which can lead to renal ischemia and kidney dysfunction.
Although cell culture steps may provide increased cell number, purity, and maturity, they do so at a cost.
This cost can include one or more of the following technical difficulties: loss of cell function due to cell aging, loss of potentially useful non-stem cell populations, delays in potential application of cells to patients, increased monetary cost, and increased risk of contamination of cells with environmental microorganisms during culture.
Suitable methods for harvesting adipose derived stem cells, however, are lacking in the art.
The existing methods suffer from a number of shortcomings.
For example, the existing methods may lack partial or full automation, a partial or completely closed system, disposability of components, etc.

Method used

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  • Methods of using regenerative cells in the treatment of peripheral vascular disease and related disorders
  • Methods of using regenerative cells in the treatment of peripheral vascular disease and related disorders
  • Methods of using regenerative cells in the treatment of peripheral vascular disease and related disorders

Examples

Experimental program
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example 1

Expression of Angiogenic Growth Factor, VEGF, by Regenerative Cells

[0192]Vascular Endothelial Growth Factor (VEGF) is one of the key regulators of angiogenesis (Nagy et al., 2003; Folkman, 1995). Placenta Growth Factor, another member of the VEGF family, plays a similar role in both angiogenesis as well as arteriogenesis. Specifically, transplant of wild-type (PlGF+ / +) cells into a PlGF knockout mouse restores ability to induce rapid recovery from hind limb ischemia (Scholz et al., 2003).

[0193]Given the importance of angiogenesis and arteriogenesis to the revascularization process, PlGF and VEGF expression by the regenerative cells of the present invention was examined using an ELISA assay (R&D Systems, Minneapolis, Minn.) using adipose derived regenerative cells from three donors. One donor had a history of hyperglycemia and Type 2 diabetes (a condition highly associated with microvascular and macrovascular disease). Regenerative cells from each donor were plated at 1,000 cells / cm2...

example 2

Regenerative Cells Contain Cell Populations that Participate in Angiogenesis

[0196]Endothelial cells and their precursors, endothelial progenitor cells (EPCs), are known to participate in angiogenesis. To determine whether EPCs are present in adipose derived regenerative cells, human adipose derived regenerative cells were evaluated for EPC cell surface markers, e.g., CD-34.

[0197]ADCs were isolated by enzymatic digestion of human subcutaneous adipose tissue. ADCs (100 ul) were incubated in phosphate saline buffer (PBS) containing 0.2% fetal bovine serum (FBS), and incubated for 20 to 30 minutes at 4° C. with fluorescently labeled antibodies directed towards the human endothelial markers CD-31 (differentiated endothelial cell marker) and CD-34 (EPC marker), as well as human ABCG2 (ATP binding cassette transporter), which is selectively expressed on multipotent cells. After washing, cells were analyzed on a FACSAria Sorter (Beckton Dickenson-Immunocytometry). Data acquisition and analy...

example 3

In Vitro Development of Vascular Structures in Regenerative Cells

[0200]An art-recognized assay for angiogenesis is one in which endothelial cells grown on a feeder layer of fibroblasts develop a complex network of CD31-positive tubes reminiscent of a nascent capillary network (Donovan et al., 2001). Since adipose derived regenerative cells contain endothelial cells, EPCs and other stromal cell precursors, we tested the ability of these regenerative cells to form capillary-like structures in the absence of a feeder layer. Regenerative cells obtained from inguinal fat pads of normal mice developed capillary networks two weeks after culture (FIG. 18A). Notably, regenerative cells from hyperglycemic mice with streptozotocin (STZ)-induced Type 1 diabetes eight weeks following administration of STZ formed equivalent capillary networks as those formed by cells from normal mice (FIG. 18B).

[0201]In a subsequent study, adipose derived regenerative cells were cultured in complete culture mediu...

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Abstract

Cells present in adipose tissue are used to treat patients, including patients with PVD and related diseases or disorders. Methods of treating patients include processing adipose tissue to deliver a concentrated amount of stem cells obtained from the adipose tissue to a patient. The methods may be practiced in a closed system so that the stem cells are not exposed to an external environment prior to being administered to a patient. Accordingly, in a preferred method, cells present in adipose tissue are placed directly into a recipient along with such additives necessary to promote, engender or support a therapeutic benefit.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to and is a continuation of U.S. application Ser. No. 12 / 494,211, filed Jun. 29, 2009, entitled “METHODS OF USING REGENERATIVE CELLS IN THE TREATMENT OF PERIPHERAL VASCULAR DISEASE AND RELATED DISORDERS,” to Fraser, et al., which is a continuation of and claims the benefit of priority to U.S. application Ser. No. 10 / 884,871, filed on Jul. 1, 2004, which is a continuation-in-part application of and claims the benefit of priority to U.S. application Ser. No. 10 / 316,127, filed on Dec. 9, 2002, entitled SYSTEMS AND METHODS FOR TREATING PATIENTS WITH PROCESSED LIPOASPIRATE CELLS, which claims the benefit of priority to U.S. Provisional Application No. 60 / 338,856, filed Dec. 7, 2001. U.S. application Ser. No. 10 / 884,871 also claims priority to U.S. Provisional Application No. 60 / 503,589 entitled METHODS OF USING ADIPOSE TISSUE-DERIVED CELLS IN THE TREATMENT OF PERIPHERAL VASCULAR DISEASE AND RELAT...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K35/12A61P37/06A61P29/00A61P9/00A61P9/10A61K35/28A61K35/44A61K45/00
CPCA61K9/0019A61L27/3834A61L27/3886A61L2430/36A61K35/44C12N5/0667C12N5/069C12N2506/1384A61K35/28C12M47/04A61P9/00A61P9/10A61P29/00A61P37/06A61K45/06A61L2300/64A61L2430/00
InventorFRASER, JOHN K.HEDRICK, MARC H.DANIELS, ERIC
OwnerLOREM VASCULAR PTE LTD