Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation.
Several human and experimental autoimmune diseases, including the current model for multiple sclerosis (MS), ie relapsing experimental autoimmune encephalomyelitis (R-EAE), have been reported to respond with complete remission to lympho- and myeloablation and rescue with transplantation of bone marrow (BMT) from healthy donors. Since treatment with autologous BM was as effective in our arthritis model as treatment with allogeneic BM from healthy rats, and in view of the much lower risk of autologous BMT in clinical practice, we have investigated treatment of R-EAE with pseudo-autologous (PSA) BM. PSABM is harvested from animals in the same active stage of R-EAE as the syngeneic recipients which are to be treated. Our results show that PSABM is as effective as syngeneic BM, except for a higher incidence of artificially induced relapses. We also demonstrated that lymphocytes present in the autologous BM graft may contribute to the occurrence of relapses post-transplantation. The implications of our results for a possible clinical application in the treatment of MS patients are discussed. If such treatment is envisaged, the use of T cell-depleted autografts seems mandatory, particularly as human BM contains 10 times more lymphocytes than rat BM.
van Gelder
M
M
Introgene BV, Rijswijk, The Netherlands.
van Bekkum
D W
DW
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D008212:Lymphocyte Depletion; D011828:Radiation Chimera; D051381:Rats; D011915:Rats, Inbred BUF; D012008:Recurrence; D012074:Remission Induction; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
D003520:Cyclophosphamide