Augmentation of organ function

• US 20070116679A1
• Filed: 06/30/2006
• Published: 05/24/2007
• Est. Priority Date: 12/29/1999
• Status: Abandoned Application

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Atala, Anthony
• Application Number:
  US11/479,252
• Publication Number:
  US 20070116679A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• 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 2430/26 for kidney reconstruction
• CPC Class Codes: A61L 27/3641 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 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• 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: A61P 13/12 of the kidneys
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2502/28 Vascular endothelial cells
• CPC Class Codes: C12N 2503/04 Screening or testing on artificial tissues
• CPC Class Codes: C12N 2533/52 Fibronectin; Laminin
• 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 5/0685 Bladder epithelial cells
• CPC Class Codes: C12N 5/0686 Kidney cells

Abstract

The present invention provides methods and compositions for augmenting organ functions using small-scale matrix implants generated by seeding tissue-specific or undifferentiated cells onto a matrix materials (e.g., a wafer, sponge, or hydrogel). The seeded matrix composition can then be implanted and will develop into an organ-supplementing structure in vivo. Continued growth and differentiation of the seeded cells on the implanted matrix results in the formation of a primitive vascular system in the tissue. The primitive vascular system can then develop into a mature vascular system, and can also support the growth and development of additional cultured cell populations. The seeded matrix system can be used to introduce a variety of different cells and tissues in vivo.

Claims

1. A kidney function augmenting construct comprising a three-dimensional biomatrix formed by seeding a matrix material with at least one population of cultured cells, such that the cells attach to the matrix and produce a tissue layer capable of augmenting native kidney function.

2. The construct of claim 1, wherein said at least one population of cells is a population of renal cells and the tissue layer differentiates into a nephron structure, or a part of a nephron structure.

3. The construct of claim 1, wherein the construct is formed by seeding cells onto a matrix material wherein the greatest dimension of the matrix material is less than 50 millimeters.

4. The construct of claim 1, wherein the matrix material is decellularized tissue.

5. The construct of claim 1, wherein the matrix material is a hydrogel.

6. The construct of claim 1, wherein the matrix material is a polymer.

7. The construct of claim 1, wherein the matrix is a substantially flat structure having a ratio of its greatest dimension to its thickness of greater than 5:

1.

8. The construct of claim 1, further comprising seeding said matrix material with a population of endothelial cells, such that the endothelial cells attach to the matrix to produce an endothelial tissue layer comprising a vascular system, wherein the endothelial cell population is seeded prior to seeding said at least one population of cells.

9. A method for augmenting the native function of a kidney comprising:

a) seeding at least one population of cultured cells on or into a matrix material, such that cells attach to the matrix material;

b) culturing the cells in the matrix material to produce a tissue layer capable of differentiating into an artificial kidney construct, thereby producing a three-dimensional biomatrix; and

c) implanting the three-dimensional biomatrix into at least one target site in the kidney, such that the tissue layer of the three-dimensional biomatrix differentiates to provide a gain of native function to the kidney, thereby augmenting native kidney function at the target site.

11. The method of claim 9, further comprising seeding said matrix material with a population of endothelial cells, such that the endothelial cells attach to the matrix to produce an endothelial tissue layer comprising a vascular system, wherein the endothelail cell population is seeded prior to seeding said at least one population of cells.

10. A method for augmenting the native function of a kidney comprising:

a) forming a plurality of three-dimensional biomatrices by seeding a plurality of matrix materials with at least one population of cultured cells;

b) culturing the cells to produce a tissue layer capable of differentiating; and

c) implanting the plurality of three-dimensional biomatrices into multiple target sites in the kidney, such that the plurality of three-dimensional biomatrices differentiate to provide a gain of native function to the kidney thereby augmenting native kidney function at the multiple target sites.

12. The method of claim 10, further comprising seeding said plurality of matrix materials with a population of endothelial cells, such that the endothelial cells attach to the matrix to produce an endothelial tissue layer comprising a vascular system, wherein the endothelail cell population is seeded prior to seeding said at least one population of cells.

13. The method of claim 9 or 10, wherein the greatest dimension of the matrix is less than 50 millimeters.

14. The method of claim 9 or 10, wherein the matrix is a substantially flat structure having a ratio of its greatest dimension to its thickness of greater than 5:

1.

15. The method of claim 9 or 10, wherein the matrix is decellularized tissue.

16. The method of claim 9 or 10, wherein the matrix is a hydrogel.

17. The method of claim 9 or 10, wherein the matrix is a polymer.

18. The method of claim 9 or 10, wherein the at least one population of cells is a population of renal cells, said renal cells producing a tissue layer that differentiates into a nephron structure, or a part of a nephron structure.

19. The method of claim 18, wherein the renal cells are an isolated population of cells selected from the group consisting of glomeruli cells, proximal tubule cells, distal tubule cells, loop of Henle cells, and collecting duct cells.

20. The method of claim 18, wherein the renal cells comprise a mixed population of cells selected from the group consisting of glomeruli cells, proximal tubule cells, distal tubule cells, loop of Henle cells, and collecting duct cells.

21. The method of claim 18, wherein the nephron structure consists of the glomerulus, distal tubules, proximal tubules, loop of Henle and collecting ducts.

22. The method of claim 18, wherein the part of the nephron structure comprises at least one renal structure selected from the group consisting of the glomerulus, distal tubules, proximal tubules, loop of Henle and collecting ducts.