ACTIVATED MESENCHYMAL STEM CELLS FOR THE PREVENTION AND REPAIR OF INFLAMMATORY STATES
Inflammatory cytokines e.g. IFN-γ serve as initiating stimuli for MSC immunosuppressive activity in vivo. Other inflammatory cytokines, such as TNF alpha, the molecule hemoxygenase I, and TLR ligation of MSC may also provide such a response.
1 . A method to prevent graft versus host disease in a mammal as result of a transplant, the method comprising:
(a) activating mammalian mesenchymal stem cells with IFN-γ; and
(b) administering the activated mammalian stem cells to the mammal who will host the graft.
2 . The method of claim 1 , wherein the activating is by a high dose of interferon gamma/ml.
3 . The method of claim 2 wherein the high dose is greater than 50 units interferon gamma/ml.
4 . The method of claim 3 wherein the high dose is about 2,000 or up to 20,000 for 2 hour units.
5 . The method of claim 1 , wherein the mesenchymal stem cells are from bone marrow.
6 . The method of claim 5 , wherein the bone marrow is human bone marrow.
7 . The method of claim 2 wherein activating is achieved by at least 2 successive pulses of exposure to >50 units/ml IFN-γ.
8 . The method of claim 3 wherein high doses are 500 units for 6 days.
9 . The method of claim 1 , wherein administering is approximately at the time of, or after, the transplant.
10 . (canceled)
11 . A method of initiating angiogenesis in a mammal comprising:
(a) obtaining a composition of human mesenchymal stem cells activated by an inflammatory cytokine; and
(b) administering the composition to a mammal need of tissue regeneration or organ repair.
12 . A method to produce activated mesenchymal stem cells for use in tissue transplantation, the method comprising:
(a) obtaining mesenchymal stem cells; and
(b) activating the mesenchymal stem cells by culturing the cells with IFN-γ.
13 . A composition of human mesenchymal stem cells activated by an inflammatory cytokine.
14 . The composition of claim 13 wherein the inflammatory cytokine is IFN-γ.
15 . (canceled)
16 . The composition of claim 13 , wherein the stem cells are activated with a dose greater than 50 units interferon gamma/ml.
17 . The composition of claim 16 , wherein stem cells are activated by at least 2 successive pulses of exposure to >50 units/ml IFN-γ within a 1-7 day period.
18 . The composition of claim 13 , wherein the mesenchymal stem cells are from bone marrow.
19 . The composition of claim 18 , wherein the bone marrow is human bone marrow.
20 . The composition of claim 13 that prevents graft versus host disease in a mammal as result of a transplant.
21 . A pharmaceutical composition comprising the composition of claim 13 that prevents graft versus host disease in a mammal as result of a transplant.