METHODS FOR GENERATING PANCREATIC TISSUE

• US 20130084266A1
• Filed: 10/29/2010
• Published: 04/04/2013
• Est. Priority Date: 10/29/2009
• Status: Abandoned Application

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Ott, Harald C., Conrad, Claudius
• Application Number:
  US13/504,358
• Publication Number:
  US 20130084266A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2502/11 blood or immune system cells
• CPC Class Codes: C12N 2502/1352 Mesenchymal stem cells
• CPC Class Codes: C12N 2502/1358 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 2502/22 pancreatic cells
• 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 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

This document provides methods and materials related to tissue generation. For example, methods for generating pancreatic tissue and providing a population of hormone-secreting cells, e.g., insulin-producing cells in a human subject are provided.

Claims

1. A method for generating a functional bioartificial pancreatic tissue, the method comprising:

providing a decellularized pancreatic tissue matrix comprising vasculature;

directly seeding the decellularized pancreatic tissue matrix with one or both of a hormone secreting cell and a regenerative cell;

seeding the matrix with an endothelial cell by vascular perfusion; and

maintaining the seeded matrix under conditions and for a time sufficient for tissue growth to occur,

thereby generating a functional bioartificial pancreatic tissue.

2. The method of claim 1, further comprising assaying for hormone secretion from the tissue.

3. The method of claim 1, wherein the hormone secreting cells secrete insulin.

4. The method of claim 3, further comprising assaying for insulin secretion from the tissue.

5. The method of claim 1, wherein providing a decellularized pancreatic tissue matrix comprises obtaining tissue comprising a pancreas or a portion thereof comprising vasculature, and decellularizing the pancreas or portion thereof under conditions such that the acellular tissue matrix, including the vasculature, substantially retains morphology of an extracellular matrix of the pancreatic tissue prior to decellularization.

6. The composition of claim 1, wherein the regenerative cell is a mesenchymal stem cell.

7. The composition of claim 1, wherein the regenerative cell is an autologous stem cell.

8. The composition of claim 1, wherein the regenerative cell is an induced pluripotent stem cell or human embryonic stem cell.

9. The composition of claim 1, wherein the endothelial cell is a human umbilical vein endothelial cell.

10. The composition of claim 1, wherein the islet cell secretes a hormone selected from the group consisting of insulin, glucagon, pancreatic polypeptide, amylin, ghrelin, and somatostatin

11. The composition of claim 8, wherein the islet cell secretes insulin or glucagon.

12. The composition of claim 1, wherein the hormone secreting cells is an islet cell.

13. The composition of claim 12, wherein the islet cell is in an intact or partially intact islet of Langerhans.

14. The composition of claim 12, wherein the islet cell is an alpha, beta, delta, PP, or epsilon cell.

15. The composition of claim 1, wherein the seeded matrix is maintained in vitro for 2-14 days or longer.

16. A functional bioartificial pancreatic tissue provided by the method of claim 1.

17. A functional bioartificial pancreatic tissue of claim 16 for the treatment of insulin-dependent diabetes.

18. A method of providing insulin-producing cells to a human subject, the method comprising obtaining a functional bioartificial pancreatic tissue provided by the method of claim 1, and transplanting the tissue into the human subject.

19. The method of claim 18, wherein one or more of the regenerative cell, the insulin producing cell, and the endothelial cell are autologous to the subject.