Treatment of autoimmune disorders by hemopoietic cell transplantation

Abstract

Abstract We have previously found that allogeneic BMT can be used to treat autoimmune diseases using various animal models for autoimmune diseases (Proc. Natl. Acad. Sci. USA 82:2483, 1985, etc.). However, in MRL/lpr mice that are radiosensitive (less than 8.5Gy), conventional BMT was found to have transient effects; the autoimmune diseases recur 3 months after BMT. However, we have found that the combination of BMT plus bone grafts (to recruit donor stromal cells) completely prevents the recurrence of autoimmune diseases in these mice (J. Immunol. 152: 3119, 1994). In addition, we have found that this strategy has no effect on the treatment of autoimmune diseases in MRL/lpr mice, since these mice become more radiosensitive after the onset of lupus nephritis, due to uremic enterocolitis. We have very recently discovered a new safe strategy for the treatment of autoimmune diseases which includes fractionated irradiation (5.5 Gy × 2) (day−1) followed by portal venous (P.V.) injection (day 0) plus intravenous (I.V.) injection (day 5) of donor bone marrow cells. We have succeeded in treating autoimmune diseases in MRL/lpr mice by this strategy; 100% of thus-treated MRL/lpr mice survive more than one year after the treatment (Blood 95: 1862, 2000). We have also found that this strategy is applicable to organ allografts in mice; all the skin and pancreas allografts survive more than one year after transplantation without using immunosuppressants. We clarify the mechanisms underlying the advantages of this strategy, and also show using cynomolgus monkeys that this strategy will become applicable to humans.