Treatment of peripheral vascular disease using umbilical cord tissue-derived cells

Patent metadata

Field	Value
Publication number	US-9585918-B2
Application number	US-201514846573-A
Country	US
Kind code	B2
Filing date	Sep 4, 2015
Priority date	Dec 28, 2005
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

Compositions and methods of using cells derived from umbilical cord tissue, to stimulate and support angiogenesis, to improve blood flow, to regenerate, repair, and improve skeletal muscle damaged by a peripheral ischemic event, and to protect skeletal muscle from ischemic damage in peripheral vascular disease patients are disclosed. In particular, methods of treating a patient having a peripheral vascular disease by systemic administration of umbilical derived cells are disclosed.

First claim

What is claimed is:

1. A method of treating peripheral ischemia comprising systemically administering an isolated homogenous population of cells obtained from human umbilical cord tissue in an amount effective to treat the peripheral ischemia, wherein the umbilical cord tissue is substantially free of blood, and wherein said isolated homogenous population of the cells is capable of self-renewal and expansion in culture, has the potential to differentiate and further has the following characteristics:
(a) expresses oxidized low density lipoprotein receptor 1, chemokine receptor ligand 3, and granulocyte chemotactic protein;
(b) does not express CD117, CD31, CD34, or CD45;
(c) expresses, relative to a human fibroblast, mesenchymal stem cell, or iliac crest bone marrow cell, increased levels of interleukin 8 and reticulon 1;
(d) has the potential to differentiate into cells of at least a skeletal muscle, vascular smooth muscle, pericyte or vascular endothelium phenotype; and
(e) expresses CD10, CD13, CD44, CD73, and CD90.

2. The method of claim 1 , wherein the step of administering comprises intravenous administration.

3. The method of claim 1 , wherein the isolated population of cells is induced in vitro to differentiate into a skeletal muscle, vascular muscle, pericyte or vascular endothelium lineage prior to administration.

4. The method of claim 1 , wherein the population of cells is genetically engineered to produce a gene product that promotes treatment of peripheral ischemia.

5. The method of claim 1 , wherein the method further comprises administering an agent selected from the group consisting of an antithrombogenic agent, an immunosuppressive agent, an immunomodulatory agent, a pro-angiogenic, an antiapoptotic agent and mixtures thereof.

6. The method of claim 1 , wherein the method further comprises administering at least one other cell type.

7. The method of claim 6 , wherein the other cell type is a skeletal muscle cell, a skeletal muscle progenitor cell, a vascular smooth muscle cell, a vascular smooth muscle progenitor cell, a pericyte, a vascular endothelial cell, a vascular endothelium progenitor cell or other multipotent or pluripotent stem cell.

8. The method of claim 1 , wherein the population of cells exerts a trophic effect.

9. The method of claim 8 , wherein the trophic effect is proliferation of vascular endothelial cells.

10. The method of claim 1 , wherein the population of cells induces migration of vascular endothelial cells and/or vascular endothelium progenitor cells to the sites of the peripheral ischemia.

11. The method of claim 1 , wherein the population of cells induces migration of vascular smooth muscle cells and/or vascular smooth muscle progenitor cells to the sites of the peripheral ischemia.

12. The method of claim 1 , wherein the population of cells induces migration of pericytes to the sites of the peripheral ischemia.

13. A method of improving blood flow in ischemic tissue in a patient having peripheral ischemia, comprising systemically administering an isolated homogenous population of cells obtained from human umbilical cord tissue in an amount effective to improve the blood flow, wherein the umbilical cord tissue is substantially free of blood, and wherein said isolated homogenous population of the cells is capable of self-renewal and expansion in culture, has the potential to differentiate and further has the following characteristics:
(a) expresses oxidized low density lipoprotein receptor 1, chemokine receptor ligand 3, and granulocyte chemotactic protein;
(b) does not express CD117, CD31, CD34, or CD45;
(c) expresses, relative to a human fibroblast, mesenchymal stem cell, or iliac crest bone marrow cell, increased levels of interleukin 8 and reticulon 1;
(d) has the potential to differentiate into cells of at least a skeletal muscle, vascular smooth muscle, pericyte or vascular endothelium phenotype; and
(e) expresses CD10, CD13, CD44, CD73, and CD90.

14. The method of claim 13 , wherein the step of administering comprises intravenous administration.

15. The method of claim 13 , wherein the method further comprises administering an agent selected from the group consisting of an antithrombogenic agent, an immunosuppressive agent, an immunomodulatory agent, a pro-angiogenic, an antiapoptotic agent and mixtures thereof.

16. The method of claim 13 , wherein the method further comprises administering at least one other cell type.

17. The method of claim 16 , wherein the other cell type is a skeletal muscle cell, a skeletal muscle progenitor cell, a vascular smooth muscle cell, a vascular smooth muscle progenitor cell, a pericyte, a vascular endothelial cell, a vascular endothelium progenitor cell or other multipotent or pluripotent stem cell.

18. The method of claim 13 , wherein the population of cells exerts a trophic effect.

19. The method of claim 18 , wherein the trophic effect is proliferation of vascular endothelial cells.

20. The method of claim 13 , wherein the population of cells induces migration of pericytes to the sites of the peripheral ischemia.

Assignees

• Depuy Synthes Products Inc

Inventors

• Buensuceso Charito S
• Kihm Anthony J
• Dhanaraj Sridevi
• Atlas Roee
• Nur Israel
• Meidler Roberto
• Bar Liliana

Classifications

• C12N2510/00

  Genetically modified cells · CPC title

• A61K38/363

  Fibrinogen · CPC title

• A61L27/3895

  using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions · CPC title

• C12N5/0605

  Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title