Preservation of pancreatic islet grafts in the extrahepatic space

Patent metadata

Field	Value
Publication number	US-11951136-B2
Application number	US-201816772078-A
Country	US
Kind code	B2
Filing date	Dec 12, 2018
Priority date	Dec 12, 2017
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

Provided herein, inter alia, are methods and compositions for treating diabetes mellitus comprising co-transplantation of an insulin-producing cell and a cell derived from a parathyroid gland (PTG), a CD34+ cell derived from a parathyroid gland, a CD34+ cell derived from a stem cell, or other progenitor cell-derived CD34+ cell.

First claim

We claim:

1. A method for treating diabetes mellitus in an individual in need thereof, comprising administering to the individual a transplant comprising:
(a) an insulin-producing cell, and
(b) a cell selected from (i) a cell derived from a parathyroid gland (PTG) and (ii) a CD34+ cell, wherein the cell produces one or more factors selected from a proangiogenic factor, a PTG hormone, and a combination thereof,
thereby treating the diabetes mellitus.

2. The method of claim 1 , wherein the insulin-producing cell is differentiated from a stem cell.

3. The method of claim 1 , wherein the insulin-producing cell is a stem cell-derived insulin-producing cell (SCIPC) or a stem cell-derived enhanced beta cluster (eBC).

4. The method of claim 1 , wherein the insulin-producing cell is a pancreatic islet beta cell.

5. The method of claim 1 , wherein the one or more factors is selected from vascular endothelial growth factor VEGF), platelet-derived growth factor (PDGF), angiopoietin, gamma-aminobutyric acid GABA), parathormone (PTH), PTH-related peptide (PTHrP), and a combination thereof.

6. The method of claim 1 , wherein the transplant is administered to an extrahepatic site.

7. The method of claim 6 , wherein the extrahepatic site is subcutaneous or intramuscular.

8. The method of claim 1 , wherein the transplant is administered using a catheter, a cannula, a syringe, or an implantable device.

9. The method of claim 1 , wherein the diabetes mellitus is type 1 diabetes, type 2 diabetes, or surgical diabetes.

10. The method of claim 1 , wherein the cell is a cell derived from PTG.

11. The method of claim 1 , wherein the cell is a CD34+ cell.

12. A method for treating diabetes mellitus in an individual in need thereof, comprising administering to the individual a transplant comprising:
(a) an insulin-producing cell,
(b) a cell that produces one or more PTG hormones; and
(c) a cell that produces one or more proangiogenic factors, thereby treating the diabetes mellitus.

13. The method of claim 12 , wherein the insulin-producing cell is differentiated from a stem cell.

14. The method of claim 12 , wherein the insulin-producing cell is a SCIPC or a stem cell-derived eBC.

15. The method of claim 12 , wherein the insulin-producing cell is a pancreatic islet beta cell.

16. The method of claim 12 , wherein the cell that produces one or more PTG hormones is derived from PTG.

17. The method of claim 12 , wherein the one or more PTG hormones is selected from GABA, PTH, PTHrP, and a combination thereof.

18. The method of claim 12 , wherein the one or more PTG hormones comprises PTH.

19. The method of claim 12 , wherein the cell that produces one or more proangiogenic factors is a CD34+ cell.

20. The method of claim 12 , wherein the one or more proangiogenic factors is selected from VEGF, PDGF, angiopoietin, and a combination thereof.

21. The method of claim 12 , wherein the transplant is administered to an extrahepatic site.

22. The method of claim 12 , wherein the extrahepatic site is subcutaneous or intramuscular.

23. The method of claim 12 , wherein the transplant is administered using a catheter, a cannula, a syringe, or an implantable device.

24. The method of claim 12 , wherein the diabetes mellitus is type 1 diabetes, type 2 diabetes, or surgical diabetes.

Assignees

• Univ California
• U S Government Represented By The Dept Of Veterans Affairs
• Us Gov Veterans Affairs

Inventors

• Ward Casey
• Tang Qizhi
• Stock Peter
• Faleo Gaetano
• Nair Gopika
• Hebrok Matthias
• Chang Wenhan
• Vo Thuy
• Bluestone Jeffrey A
• De Klerk Eleonora

Classifications

• A61K35/55 Primary

  Glands not provided for in groups A61K35/22 - A61K35/545, e.g. thyroids, parathyroids or pineal glands · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/0024

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• A61K35/39 Primary

  Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title