Organs for transplantation

• US 10,272,109 B2
• Filed: 01/08/2018
• Issued: 04/30/2019
• Est. Priority Date: 04/12/2013
• Status: Active Grant

• Current Assignee: Houston Methodist Hospital (Methodist Hospital)
• Original Assignee: ABT Holding Company (Athersys, Inc.)
• Inventors: La Francesca, Saverio, Ting, Anthony E., Deans, Robert J.
• Primary Examiner(s): Underdahl, Thane
• Application Number:
  US15/864,862
• Publication Number:
  US 20180325945A1
• Time in Patent Office: 477 Days
• Field of Search: None
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2500/84 from mammals
• CPC Class Codes: C12N 2502/03 non-embryonic pluripotent stem cells
• CPC Class Codes: C12N 5/0018 Culture media for cell or tissue culture media for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

The invention provides methods and compositions that improve the success of organ transplantation. The methods and compositions are directed to exposing a desired organ to stem cells prior to, during, and/or after transplantation. In one embodiment, the stem cells reduce the deleterious effects of ischemia on an organ designated to be harvested for transplantation or that has been harvested for transplantation. In another embodiment in which an organ designated for transplantation is perfused ex vivo, the method involves reducing ischemic reperfusion injury by perfusing the organ with a medium that contains stem cells.

Claims

1. A method comprising transplanting an organ that has been exposed to exogenous stem cells, wherein the stem cells are non-embryonic, non-germ cells that express telomerase, have a normal karyotype, are not tumorigenic, and wherein the stem cells have undergone at least 10-40 cell doublings in cell culture prior to their exposure to the organ, wherein the organ is exposed to the stem cells prior to transplantation into a recipient.

2. The method of claim 1, wherein the stem cells can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.

3. The method of claim 1, wherein the stem cells express oct4.

4. The method of claim 2, wherein the stem cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers.

5. The method of claim 1, wherein the stem cells are non-embryonic, non-germ cells that express oct4 and telomerase and can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.

6. The method of claim 5, wherein the stem cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers.

7. The method of claim 5 or 6, wherein the stem cells are non-HLA matched, allogeneic cells.

8. The method of claim 1, wherein the stem cells have undergone at least 30-35 cell doublings.

9. The method of claim 1, wherein the concentration of stem cells exposed to the organ is about 1×

10⁶ cells/ml to about 10×

10⁶ cells/ml.

10. The method of claim 1, wherein the stem cells are exposed to the organ for about 2-4 hours.

11. The method of claim 1, wherein the stem cells are contained in a fluid for perfusion into the organ or in a carrier for intra-organ administration.

12. The method of claim 1, wherein the stem cells are contained in a medium in which the organ is bathed prior to transplantation.

13. The method of claim 1, wherein the organ is selected from the group consisting of lung, kidney, heart, liver, pancreas, thymus, gastrointestinal tract, and composite allografts.

14. The method of claim 1, wherein exposure to the stem cells reduces inflammation in the organ.

15. The method of claim 1, wherein exposure to the stem cells reduces the occurrence of inflammatory cells in the organ.

16. The method of claim 1, wherein exposure to the stem cells reduces inflammatory cytokines in the organ.

17. The method of claim 1, wherein exposure to the stem cells reduces ischemic-reperfusion injury.

18. The method of claim 1 wherein the stem cells are derived from human bone marrow.