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

• US 9,125,906 B2
• Filed: 08/10/2011
• Issued: 09/08/2015
• Est. Priority Date: 12/28/2005
• Status: Expired due to Fees

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Inventors: Buensuceso, Charito S., Kihm, Anthony J., Dhanaraj, Sridevi, Atlas, Roee, Nur, Israel, Meidler, Roberto, Bar, Liliana
• Primary Examiner(s): HILL, KEVIN KAI
• Application Number:
  US13/206,913
• Publication Number:
  US 20120213743A1
• Time in Patent Office: 1,490 Days
• Field of Search: 424/93.21, 424/93.7, 435/325, 435/366
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 35/34 Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 38/4833 Thrombin (3.4.21.5)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly

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 with umbilical derived cells and fibrin glue are disclosed.

Claims

1. A method of improving blood flow in ischemic tissue in a patient having peripheral ischemia, comprising administering by intramuscular injection or injection into adipose depots in muscle a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a mixture of fibrin and an isolated homogenous population of cells obtained from human umbilical cord tissue in an amount effective to improve blood flow in the ischemic tissue, 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 pharmaceutical composition is administered at the sites of peripheral ischemia.

3. The method of claim 1, wherein the pharmaceutical composition is administered locally.

4. 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.

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

6. The method of claim 1, wherein the composition further comprises 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.

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

8. The method of claim 7, 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.

9. The method of claim 1, wherein the pharmaceutical composition exerts a trophic effect.

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

11. The method of claim 1, wherein the pharmaceutical composition induces migration of vascular endothelial cells and/or vascular endothelium progenitor cells to the sites of the peripheral disease.

12. The method of claim 1, wherein the pharmaceutical composition induces migration of vascular smooth muscle cells and/or vascular smooth muscle progenitor cells to the sites of the peripheral disease.

13. The method of claim 1, wherein the pharmaceutical composition induces migration of pericytes to the sites of the peripheral vascular disease.

14. A method of improving blood flow in ischemic tissue in a patient having peripheral ischemia, comprising administering by intramuscular injection or injection into adipose depots in muscle a mixture of fibrin and an isolated homogenous population of cells obtained from human umbilical cord tissue in an amount effective to improve blood flow in the ischemic tissue, 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.

15. The method of claim 14, wherein the mixture of the population of cells and fibrin is administered at the sites of peripheral ischemia.

16. The method of claim 14, wherein the mixture of fibrin glue and the population of cells is administered locally.

17. The method of claim 14, 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.

18. The method of claim 14, wherein the population of cells is genetically engineered to produce a gene product that promotes treatment of peripheral vascular disease.

19. The method of claim 14, further comprising administration of 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.

20. The method of claim 14 further comprising administration of at least one other cell type.

21. The method of claim 20, 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.

22. The method of claim 14, wherein the population of cells exerts a trophic effect.

23. The method of claim 21, wherein the trophic effect is proliferation of vascular endothelial cells.

24. The method of claim 14, wherein the population of cells induces migration of vascular endothelial cells and/or vascular endothelium progenitor cells to the sites of the peripheral disease.

25. The method of claim 14, 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 disease.

26. The method of claim 14, wherein the population of cells induces migration of pericytes to the sites of the peripheral vascular disease.

27. A method of improving blood flow in ischemic tissue in a patient having peripheral ischemia, comprising administering by intramuscular injection or injection into adipose depots in muscle a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a mixture of fibrin glue and an isolated homogenous population of cells obtained from human umbilical cord tissue in an amount effective to improve blood flow in the ischemic tissue, wherein the umbilical cord tissue is substantially free of blood, wherein the fibrin glue comprises from about 16 to about 24 IU/ml of thrombin and from about 39.3 to about 60.7 mg/ml of fibrinogen, 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.

28. A method of improving blood flow in ischemic tissue in a patient having peripheral ischemia, comprising administering by intramuscular injection or injection into adipose depots in muscle a mixture of fibrin glue and an isolated homogenous population of cells obtained from human umbilical cord tissue in an amount effective to improve blood flow in the ischemic tissue, wherein the umbilical cord tissue is substantially free of blood, wherein the fibrin glue comprises from about 16 to about 24 IU/ml of thrombin and from about 39.3 to about 60.7 mg/ml of fibrinogen, 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.