As long ago as 1985, we discovered, using animal models for autoimmune diseases, that conventional allogeneic BMT could be used to prevent and also treat not only systemic but also organ-specific autoimmune diseases (AIDs).

Our research at that time showed that conventional allogeneic BMT could be used to prevent not only TIDM in NOD mice [1] but also lupus nephritis in lupus mice [2]. In contrast, when BMT was carried out from autoimmune-prone mice to normal mice, the chimeras showed AIDs, strongly suggesting that AIDs were derived from BM defects, since thymus grafts from autoimmune-prone mice to athymic (nu/nu) mice did not result in the development of AIDs [3]. Based on these findings, we focused our research on the BM and eventually discovered a number of BM defects [4-7].

We developed a BMT technique that combines a “PM” for collecting BMCs with the intra-bone marrow (IBM) injection of BMCs (IBM-BMT) [8] (Figure1). As distinct from the conventional AM, the PM allows rapid (within 1 h) collection of BMCs without T cell contamination (T cells<10%). Therefore, no GvHD occurs. Moreover, the burden on donors, such as back pain, bleeding and infection, can be reduced.

Figure 1: A new BMT method for allogeneic BMT. The new method consists of PM+IBM-BMT.

Full chimerism can be achieved even with only mild conditioning regimens if IBM-BMT is carried out, since IBM-BMT replaces not only the recipient’s HSCs but also MSCs with donor-derived HSCs and MSCs. The findings to date strongly suggest that all the body’s cells originate in the BM, and that all diseases might therefore originate from defects in the BM. Indeed, one paper already suggests that gastric cancer originates from BM-derived cells [9].

Finally, I would like to propose a new concept of SCDs (Figure 2). On the one hand, there are HSC disorders, which include (i) aplasia of HSCs (aplastic anemia), (ii) monoclonal or oligoclonal abnormal HSC proliferative syndromes (leukemias and myelodysplastic syndrome), and (iii) polyclonal abnormal HSC proliferative syndromes (autoimmune diseases) [10,11].

Figure 2: A novel concept of stem cell disorders.

On the other hand, there are MSC disorders, which include age associated diseases such as osteoporosis [12] and emphysema [13], Alzheimer’s disease, and atherosclerosis [8,14]; it has been proposed that autoimmune mechanisms are involved in the development of atherosclerosis [15,16] and also Alzheimer’s disease [17].

We firmly believe that the development of our BMT method heralds a revolution not only in the field of transplantation (BMT and organ transplantation) but also in the fields of cancer and regeneration.

We would like to thank Mr. Hilary Eastwick-Field and Ms. Keiko Ando for their help in the preparation of the manuscript. These studies were mainly supported by the 21st Century Center of Excellence (COE) program of the Ministry of Education, Culture, Sports, Science and Technology. The Research on Allergic Disease and Immunology Committee from Health and Labour Sciences Research Grants of the Ministry of Health, Labour and Welfare. This study was supported by Otsuka Pharmaceutical Company, Ltd.