Vascularization enhanced graft constructs

• US 7,776,596 B2
• Filed: 05/02/2003
• Issued: 08/17/2010
• Est. Priority Date: 05/02/2002
• Status: Expired due to Fees

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Badylak, Stephen F.
• Primary Examiner(s): CHEN, SHIN LIN
• Application Number:
  US10/428,358
• Publication Number:
  US 20040006395A1
• Time in Patent Office: 2,664 Days
• Field of Search: 424/93.7, 424/550, 424/558, 424/551, 435/325, 435/371, 435/373
• US Class Current: 435/373
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3826 Muscle cells, e.g. smooth muscle cells
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: C12N 2501/135 Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 2501/15 Transforming growth factor beta (TGF-β)
• CPC Class Codes: C12N 2501/165 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: C12N 2502/1347 Smooth muscle cells
• CPC Class Codes: C12N 2502/253 Bladder cells
• CPC Class Codes: C12N 2502/28 Vascular endothelial cells
• CPC Class Codes: C12N 2509/00 Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 5/0685 Bladder epithelial cells
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells
• CPC Class Codes: C12N 5/0697 Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

Abstract

A tissue graft construct for use in repairing diseased or damaged tissues is provided. The tissue graft construct comprises a matrix composition selected from the group consisting of urinary bladder submucosa and stomach submucosa, and extracts and hydrolysates thereof, added endothelial cells, and at least one additional preselected, exogenous population of cells which enhance initiation of the formation vessel-like structures in the graft construct. The preselected population of cells can be a population of non-keratinized or keratinized epithelial cells or a population of mesodermally-derived cells selected from the group consisting of fibroblasts, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, multi-potential progenitor cells, pericytes, osteogenic cells, and any other suitable cell type, preferably selected based on the tissue to be repaired. Methods for enhancing the vascularization in vivo of these tissue graft constructs and for preparing these graft constructs are also provided.

Claims

1. A tissue graft construct for use in repairing diseased or damaged tissues, said tissue graft construct comprising a matrix composition comprising a material selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue, wherein the tissue graft construct further comprises added endothelial cells, and at least one additional preselected, exogenous population of cells wherein the matrix composition is seeded with the additional preselected population of cells after the matrix composition is seeded with the endothelial cells, wherein said exogenous population of cells enhances the initiation of vessels or vessel-like structures in said graft construct.

2. The graft construct of claim 1 wherein the at least one additional preselected, exogenous population of cells comprises a population of cells selected from the group consisting of keratinized epithelial cells, non-keratinized epithelial cells, and mesodermally-derived cells.

3. The graft construct of claim 1 wherein the at least one additional preselected, exogenous population of cells comprises a population of smooth muscle cells.

4. The graft construct of claim 1 wherein the at least one additional preselected, exogenous population of cells comprises a population of smooth muscle cell progenitor cells.

5. The graft construct of claim 1 wherein the urinary bladder or stomach submucosa tissue is delaminated from the tunica muscularis layer and at least the luminal portion of the tunica mucosa layer of said submucosa tissues.

6. The graft construct of claim 1 wherein the exogenous population of cells is a population of fibroblasts.

7. A tissue graft construct for use in repairing diseased or damaged tissues, said tissue graft construct comprising a matrix composition comprising a material selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue, wherein the tissue graft construct further comprises added endothelial cells, and at least one additional preselected, exogenous population of cells and wherein the matrix composition is seeded with the endothelial cells after the matrix composition is seeded with the additional preselected population of cells.

8. The graft construct of claim 7 wherein the at least one additional cell population comprises a population of cells selected from the group consisting of keratinized epithelial cells, non-keratinized epithelial cells, mesodermally-derived cells, smooth muscle cells, and smooth muscle cell progenitor cells.

9. The graft construct of claim 7 wherein the exogenous population of cells is a population of fibroblasts and the material is selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue.

10. The graft construct of claim 9 wherein the urinary bladder or stomach submucosa tissue is delaminated from the tunica muscularis layer and at least the luminal portion of the tunica mucosa layer of said submucosa tissues.

11. A tissue graft construct for use in repairing diseased or damaged tissues, said tissue graft construct comprising a matrix composition comprising a material selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue, wherein the tissue graft construct further comprises added endothelial cells, and at least one additional preselected, exogenous population of cells and wherein the matrix composition is seeded with the endothelial cells and the additional preselected population of cells simultaneously or nearly simultaneously.

12. The graft construct of claim 11 wherein the at least one additional cell population comprises a population of cells selected from the group consisting of keratinized epithelial cells, non-keratinized epithelial cells, mesodermally-derived cells, smooth muscle cells, and smooth muscle cell progenitor cells.

13. The graft construct of claim 11 wherein the exogenous population of cells is a population of fibroblasts and the material is selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue.

14. The graft construct of claim 13 wherein the urinary bladder or stomach submucosa tissue is delaminated from the tunica muscularis layer and at least the luminal portion of the tunica mucosa layer of said submucosa tissues.

15. A tissue graft construct having vessel-like structures for use in repairing diseased or damaged tissues, said tissue graft construct comprising a matrix composition comprising a material selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue, wherein the tissue graft construct further comprises added endothelial cells, and at least one additional preselected, exogenous population of cells wherein said at least one additional preselected, exogenous population of cells enhances the initiation of formation of said vessel-like structures in said graft construct.

16. The graft construct of claim 15 further comprising a heparinase.

17. The graft construct of claim 15 further comprising a growth factor selected from the group consisting of vascular endothelial cell-derived growth factor, platelet-derived growth factor, a platelet-derived growth factor-like molecule, transforming growth factor β

, and a serum growth factor.

18. The graft construct of claim 15 wherein the at least one additional cell population comprises a population of cells selected from the group consisting of keratinized epithelial cells, non-keratinized epithelial cells, mesodermally-derived cells, smooth muscle cells, and smooth muscle cell progenitor cells.

19. The graft construct of claim 15 wherein the exogenous population of cells is a population of fibroblasts and the material is selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue.

20. The graft construct of claim 19 wherein the urinary bladder or stomach submucosa tissue is delaminated from the tunica muscularis layer and at least the luminal portion of the tunica mucosa layer of said submucosa tissues.

21. A method of preparing a tissue graft construct having vessel-like structures for use in repairing diseased or damaged tissues, said method comprising the step of seeding in vitro a matrix composition comprising a material selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue, with a population of endothelial cells, and at least one additional preselected, exogenous population of cells wherein said at least one additional preselected, exogenous population of cells enhances the initiation of formation of said vessel-like structures in said graft construct.

22. The method of claim 21 wherein the at least one additional cell population comprises a population of cells selected from the group consisting of keratinized epithelial cells, non-keratinized epithelial cells, mesodermally-derived cells, smooth muscle cells, and smooth muscle cell progenitor cells.

23. The method of claim 21 wherein the exogenous population of cells is a population of fibroblasts and the material is selected from the group consisting of urinary bladder submucosa tissue and stomach submucosa tissue.

24. The method of claim 23 wherein the urinary bladder or stomach submucosa tissue is delaminated from the tunica muscularis layer and at least the luminal portion of the tunica mucosa layer of said submucosa tissues.

25. The method of claim 21 wherein the graft construct further comprises a heparinase.

26. The method of claim 21 wherein the graft construct further comprises a growth factor selected from the group consisting of vascular endothelial cell-derived growth factor, platelet-derived growth factor, a platelet-derived growth factor-like molecule, transforming growth factor β

, and a serum growth factor.