Allogeneic mesenchymal stem cells for treatment of experimental autoimmune encephalomyelitis.
The use of allogeneic "universal donor" mesenchymal stromal cells (MSCs) may be a substantial clinical convenience for treatment of autoimmune ailments such as multiple sclerosis. We therefore tested whether allogeneic MSCs can be exploited for treatment of experimental autoimmune encephalomyelitis (EAE) in mice with otherwise intact immune system. Administration of allogeneic Balb/c-derived MSCs to C57Bl/6 mice with pre-established EAE led to a significant decrease in disease score over time comparable to that achieved with syngeneic MSCs, and was correlated with a significant blunting of immune cell infiltration to the spinal cord and reduced circulating levels of interferon-gamma (IFN-gamma) and interleukin-17. Pretreatment of allogeneic MSCs with IFN-gamma increased the expression levels of CCL2 as well as major histocompatibility complex I (MHCI) and MHCII, but also led to complete loss of suppressive activity in vivo that correlated with immune rejection. In conclusion, allogeneic MSCs can suppress the manifestations of EAE, yet retain the potential for alloimmunization.
Rafei
Moutih
M
The Montreal Center for Experimental Therapeutics in Cancer, Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada.
Birman
Elena
E
Forner
Kathy
K
Galipeau
Jacques
J
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000628:therapy*; D005805:Genes, MHC Class I / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous / Q000379:methods*
D018932:Chemokine CCL2; D020381:Interleukin-17; D007371:Interferon-gamma