ISPO

Hematopoietic stem cell transplantation

S Ikehara, MD PhD

First Department of Pathology, Transplantation Center, Regeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan

AIM: Bone marrow transplantation (BMT) is now one of the most powerful strategies for the treatment of leukemia, aplastic anemia, congenital immunodeficiency, and also autoimmune diseases. Using various autoimmune-prone mice, we have previously shown that conventional allo BMT can be used to treat a range of autoimmune diseases (PNAS 82:2483,1985 and Exp. Hematl. [Review] 29: 661, 2001). These findings have recently been confirmed even in humans. However, in humans, the success rate of BMT across major histocompatibility complex (MHC) barriers is lowered by graft-versus-host disease (GvHD), graft rejection, and incomplete T-cell recovery. Therefore, auto BMT or peripheral blood stem cell transplantation (PBSCT) is the preferred treatment for autoimmune diseases. However, there have been reports on the recurrence or persistence of autoimmune diseases after auto BMT or PBSCT. Therefore, it is important to establish a safe new method for allo BMT. We have just established a new BMT method in which bone marrow cells (BMCs) are directly injected into the intra-bone marrow (IBM-BMT). The present study shows that “IBM-BMT” is the best strategy for allo BMT and also organ allografts to induce persistent tolerance. METHODS: As controls, BMCs were intravenously (IV) or portal venously (PV) injected for BMT (IV-BMT or PV-BMT). Using various animals (mice, rats, rabbits, and monkeys), we compared the effects of three strategies (IV-BMT, PV-BMT, and IBM-BMT) on allo BMT and organ allografts. CONCLUSION: PV-BMT was found to be more effective in treating various immune disorders than conventional IV-BMT. However, IBM-BMT was found to be much more effective than PV-BMT not only in treating various intractable diseases (including autoimmune diseases) but also in promoting the engraftment of organ allografts than PV-BMT. These findings strongly suggest that IBM-BMT would become a valuable strategy for BMT and organ transplantation even in humans.

For more information, contact ikehara@takii.kmu.ac.jp

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Molecular Genetics & Therapy - 1.

http://www.cancerprev.org/Journal/Issues/26/101/1101/4679