Organs for transplantation
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.
1. A method comprising transplanting a tissue that has been exposed ex vivo 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 tissue, wherein the tissue 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 3 , wherein the stem cells 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 1 , 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 tissue is about 1×10 6 cells/ml to about 10×10 6 cells/ml.
10. The method of claim 1 , wherein the stem cells are exposed to the tissue for about 2-4 hours.
11. The method of claim 1 , wherein the stem cells are contained in a fluid for perfusion into the tissue or in a carrier for administration to the tissue.
12. The method of claim 1 , wherein the stem cells are contained in a medium in which the tissue is bathed prior to transplantation.
13. The method of claim 1 , wherein the tissue is selected from the group consisting of cornea, skin, veins, arteries, bone, tendons and valves.
14. The method of claim 1 , wherein exposure to the stem cells reduces inflammation in the tissue.
15. The method of claim 1 , wherein exposure to the stem cells reduces the occurrence of inflammatory cells in the tissue.
16. The method of claim 1 , wherein exposure to the stem cells reduces inflammatory cytokines in the tissue.
17. The method of claim 1 , wherein exposure to the stem cells reduces ischemic-reperfusion injury in the tissue.
18. The method of any of claims 1 - 17 wherein the stem cells are derived from bone marrow.
19. The method of claim 18 wherein the stem cells are derived from human bone marrow.