Immunocompatible amniotic membrane products

Patent metadata

Field	Value
Publication number	US-10272116-B2
Application number	US-201414172940-A
Country	US
Kind code	B2
Filing date	Feb 5, 2014
Priority date	Feb 18, 2010
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

Provided herein is a placental product comprising an immunocompatible amniotic membrane. Such placental products can be cryopreserved and contain viable therapeutic cells after thawing. The placental product of the present invention is useful in treating a patient with a tissue injury (e.g. wound or burn) by applying the placental product to the injury. Similar application is useful with ligament and tendon repair and for engraftment procedures such as bone engraftment.

First claim

The invention claimed is:

1. A cryopreserved amniotic membrane comprising viable cells native to the amniotic membrane; wherein the cryopreserved amniotic membrane is immunocompatible; wherein at least 70% of the cells are viable; wherein the viable cells comprise two or more cell types consisting of MSCs, fibroblasts, and epithelial cells; wherein the cryopreserved amniotic membrane comprises less than about 1% of CD14+ macrophages.

2. The cryopreserved amniotic membrane of claim 1 , wherein the cryopreserved amniotic membrane comprises one or more therapeutic factors native to the amniotic membrane.

3. The cryopreserved amniotic membrane of claim 1 , wherein the cryopreserved amniotic membrane comprises extracellular matrix that is native to the amniotic membrane.

4. The cryopreserved amniotic membrane of claim 1 , wherein the membrane is immunocompatible by being selectively depleted in one or more types of functional immunogenic cells.

5. The cryopreserved amniotic membrane of claim 1 , wherein the amniotic membrane has a substantial decrease in TNF-α release after lipopolysaccharide (LPS) stimulation.

6. The cryopreserved amniotic membrane of claim 5 , wherein the amniotic membrane releases TN F-α in an amount less than 420 pg/ml.

7. The cryopreserved amniotic membrane of claim 1 , wherein the amniotic membrane is immunocompatible by being substantially free of immunogenic maternal cells.

8. The cryopreserved amniotic membrane of claim 7 , wherein the immunogenic maternal cells are selected from the group consisting of maternal dendritic cells, maternal leukocytes, and a combination thereof.

9. The cryopreserved amniotic membrane of claim 1 , wherein the viable cells further comprise stromal cells.

10. The cryopreserved amniotic membrane of claim 9 , wherein the stromal cells are in an amount of about 2,000 to about 15,000 per cm 2 of the amniotic membrane.

11. The cryopreserved amniotic membrane of claim 1 , wherein the cryopreserved amniotic membrane is associated with a nitrocellulose substrate/support.

12. The cryopreserved amniotic membrane of claim 1 , further comprising at least one cell-permeating cryopreservative, at least one non-cell permeating cryopreservative, derivatives thereof or a combination thereof.

13. The cryopreserved amniotic membrane of claim 12 , wherein the cell permeating cryopreservative, the non-cell-permeating cryopreservative, derivative thereof, or combination thereof is present in an amount of about 5% to about 20% by volume.

14. The cryopreserved amniotic membrane of claim 13 , wherein the cryopreservative comprises DMSO.

15. The cryopreserved amniotic membrane of claim 1 , wherein the amniotic membrane comprises MSCs and at least 40% of the MSCs are viable after a freeze-thaw cycle.

16. A previously cryopreserved membrane comprising an amniotic membrane, wherein the previously cryopreserved amniotic membrane comprises:
a) viable cells, wherein said viable cells are native to the amniotic membrane before cryopreservation and greater than 70% of said cells are viable, wherein the viable cells comprise two or more cell types consisting of MSCs, fibroblasts, and epithelial cells;
b) one or more therapeutic factors that are native to the amniotic membrane;
c) extracellular matrix that is native to the amniotic membrane; and
d) less than about 1% of CD14+ macrophages.

17. The cryopreserved amniotic membrane of claim 1 , wherein the amniotic membrane comprises an epithelial layer, a basement membrane layer, and a stromal layer, wherein all layers are from the same amniotic membrane.

18. The cryopreserved amniotic membrane of claim 17 , wherein the amniotic membrane comprises fibroblasts in an amount of about 2% to about 30% of total cells, and wherein at least 40% of the fibroblasts are viable.

19. The cryopreserved amniotic membrane of claim 17 , wherein the amniotic membrane comprises MSCs in an amount of at least about 1% to about 10% of the total cells.

20. The cryopreserved amniotic membrane of claim 17 , wherein the amniotic membrane comprises epithelial cells in an amount of at least about 40% to about 90% of the total cells.

Assignees

• Osiris Therapeutics Inc

Inventors

• Tom Samson
• Danilkovitch Alla
• Yoo Dana
• Jansen Timothy
• Kuang Jin-Qiang
• Marconi Jennifer Michelle

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61K38/1841

  Transforming growth factor [TGF] · CPC title

• C12N2502/025

  extra-embryonic cells, e.g. amniotic epithelium, placental cells, Wharton's jelly · CPC title