Tissue constructs including pancreas derived microvessel fragments and related methods

Patent metadata

Field	Value
Publication number	US-11464808-B2
Application number	US-201816609063-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	Apr 28, 2017
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

A tissue construct is provided that comprises a pancreas derived microvessel fragment and a pancreatic islet cell. The pancreas derived microvessel fragment and the pancreatic islet cell can be incorporated into a biocompatible medium. Tissue constructs can be comprised of other cells, such as stem cells, combined with the pancreas derived microvascular fragment. Methods for isolating microvessel fragments from a pancreas are also provided and include enzymatic digestion of pancreatic tissue and separation of microvessel fragments from endocrine and exocrine tissue. Methods for treating diabetes are further provided and include administration of the tissue constructs.

First claim

What is claimed is:

1. A tissue construct, comprising (i) a microvessel fragment derived from exocrine tissue of a pancreas and (ii) a pancreatic islet cell.

2. The tissue construct of claim 1 , further comprising a biocompatible medium.

3. The tissue construct of claim 2 , wherein the biocompatible medium comprises a hydrogel.

4. The tissue construct of claim 3 , wherein the hydrogel is comprised of a material selected from the group consisting of agarose, alginate, collagen, fibrinogen, fibrin, laminin, a polyoxyethylene-polyoxypropylene block copolymer, silicone, polysaccharide, polyethylene glycol, and polyurethane.

5. The tissue construct of claim 4 , wherein the hydrogel is comprised of collagen type I.

6. The tissue construct of claim 1 , wherein the microvessel fragment derived from exocrine tissue of a pancreas and the pancreatic islet cell are obtained from a human.

7. The tissue construct of claim 1 , wherein the tissue construct further comprises one or more Relevant Cells or one or more stem cells.

8. A tissue construct, comprising:
a microvessel fragment derived from exocrine tissue of a pancreas; and
one or more Relevant Cells and/or one or more stem cells.

9. The tissue construct of claim 8 , further comprising a biocompatible medium.

10. The tissue construct of claim 9 , wherein the biocompatible medium comprises a hydrogel.

11. The tissue construct of claim 10 , wherein the hydrogel is comprised of a material selected from the group consisting of agarose, alginate, collagen, fibrinogen, fibrin, laminin, a polyoxyethylene-polyoxypropylene block copolymer, silicone, polysaccharide, polyethylene glycol, and polyurethane.

12. The tissue construct of claim 11 , wherein the hydrogel is comprised of collagen type I.

13. A method for enriching microvessel fragments derived from exocrine tissue of a pancreas, comprising:
subjecting an amount of pancreatic tissue to an enzymatic digestion to produce a slurry of digested pancreatic tissue;
centrifuging the slurry of digested tissue in a first centrifuge tube at about 100 G to 200 G to deposit endocrine and exocrine tissue at the bottom of the centrifuge tube;
collecting the supernatant from the first centrifuge tube in a second centrifuge tube; and
centrifuging the supernatant at about 2000 G to pellet an amount of microvessel fragments derived from exocrine tissue of a pancreas.

14. The method of claim 13 , further comprising a step of isolating an amount of pancreatic islet cells from the pancreatic tissue.

15. A method for treating diabetes, comprising administering to a subject in need thereof an effective amount of the tissue construct of claim 1 comprising microvessel fragment derived from exocrine tissue of a pancreas and a pancreatic islet cell.

16. The method of claim 15 , wherein administering the tissue construct comprises subcutaneously administering the tissue construct.

17. The method of claim 16 , wherein subcutaneously administering the tissue construct comprises subcutaneously administering the tissue construct at multiple sites in a body of a subject.

18. The method of claim 15 , wherein the microvessel fragment derived from exocrine tissue of a pancreas and the pancreatic islet cell are incorporated into a biocompatible medium.

19. The method of claim 15 , wherein the microvessel fragment derived from exocrine tissue of a pancreas and the pancreatic islet cell are obtained from the subject.

Assignees

• Univ Louisville Res Found Inc
• Univ Of Louisville Research Foundation

Inventors

• Appakalai Balamurugan
• Williams Stuart K

Classifications

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61P3/10 Primary

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C12N2502/28

  Vascular endothelial cells · CPC title

• C12N5/0677

  Three-dimensional culture, tissue culture or organ culture; Encapsulated cells · CPC title

• C12N2513/00

  3D culture · CPC title