BLOOD VESSEL FORMATION FROM ENDOTHELIAL COLONY FORMING CELLS

• US 20080025956A1
• Filed: 08/13/2007
• Published: 01/31/2008
• Est. Priority Date: 02/09/2004
• Status: Abandoned Application

• Current Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Original Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Inventors: Yoder, Mervin, Prater, Daniel, Ingram, David
• Application Number:
  US11/837,999
• Publication Number:
  US 20080025956A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/145 Thrombopoietin [TPO]
• CPC Class Codes: C12N 2501/22 Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 2501/26 Flt-3 ligand (CD135L, flk-2 ligand)
• CPC Class Codes: C12N 2502/28 Vascular endothelial cells
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: C12N 5/0692 Stem cells; Progenitor cells; Precursor cells
• CPC Class Codes: G01N 2333/70589 CD45
• CPC Class Codes: G01N 2333/70596 Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/56966 Animal cells

Abstract

Methods and compositions to form fully functional blood vessels in vivo using endothelial colony forming cells (ECFCs) are disclosed. Culturing ECFCs in a support material results in association of ECFCs in vitro and formation of blood vessels in vivo upon implantation. Direct administration of cultured ECFCs form blood vessels in vivo. Formation of blood vessels is useful in treating a variety of medical conditions including ischemia and hypoxia.

Claims

1. A method for forming a functional vasculature in vivo in a host, the method comprising:

(a) culturing a plurality of isolated high proliferative-potential endothelial colony forming cells (HPP-ECFC) in a support material;

(b) implanting the support material comprising the endothelial colony forming cells to a target site; and

(c) forming the functional vasculature in vivo in the target site in the host.

2. The method of claim 1, wherein the support material is an artificial matrix.

3. The method of claim 2, wherein the matrix is a gel comprising one or more components selected from the group consisting of collagen, fibronectin, gelatin, laminin and any extracellular matrix constituent.

4. The method of claim 1, wherein the ECFCs are circulating ECFCs.

5. The method of claim 1, wherein the target site comprises an ischemic injury.

6. The method of claim 1, wherein the target site is selected from the group consisting of heart, lungs, kidney, liver, and pancreas.

7. The method of claim 1, wherein the host is a human.

8. The method of claim 1, wherein the target site requires vessel formation.

9. The method of claim 1, wherein the endothelial colony forming cells comprise a density of about 1-2 million cells per milliliter volume of implantation support material.

10. The method of claim 1, wherein the endothelial colony forming cells are cultured for about 12-48 hours prior to implantation.

11. The method of claim 1, wherein the support material is viscous.

12. The method of claim 1, wherein the support material provides three-dimensional cell growth.

13. The method of claim 1, wherein the support material comprising the cells is administered directly to the target site.

14. A method for forming functional blood vessels in vivo in a host, the method comprising:

(a) culturing cord blood endothelial colony forming cells (ECFCs) in vitro;

(b) administering the cultured cells to a target site; and

(c) forming the vasculature in vivo in the host.

15. An implantable scaffold for treating an ischemic injury in a host, the scaffold comprising high proliferative-potential endothelial colony forming cells (HPP-ECFC), wherein the endothelial colony forming cells associate to form blood vessels in vivo.

16. The scaffold of claim 15 comprising a growth factor.

17. An engineered tissue comprising a biologically compatible support material and a plurality of cultured high proliferative-potential endothelial colony forming cells (HPP-ECFC) that initiate vessel formation.

18. A composition comprising an effective amount of high proliferative-potential endothelial colony forming cells (HPP-ECFC) culture on a biocompatible gel material.

19. The composition of claim 19 comprises one or more components of an extra cellular matrix.

20. The composition of claim 19, wherein the ECFCs are cultured on a growth medium for endothelial cells.