A new concept of stem cell disorders and their new therapy.

The author previously proposed a new concept of categorizing stem cell disorders as: (1) stem cell aplasia (aplastic anemia), (2) monoclonal hematopoietic stem cell proliferative syndrome (leukemia and myelodysplastic syndrome), and (3) polyclonal hemopoietic stem cell proliferative syndrome (systemic and organ-specific autoimmune diseases). This review includes the following two stem cell disorders: mesenchymal stem cell disorders and organ-specific stem cell disorders. Age-associated diseases such as Alzheimer's disease, osteoporosis, and lung fibrosis belong to the former, whereas carcinosarcoma in the lung and adeno-endocrine cell carcinoma in the stomach belong to the latter. Recently, we have established a new method for allogeneic bone marrow transplantation using chimerism-resistant autoimmune-prone MRL/lpr mice. In this method, whole bone marrow cells containing a small number of T cells and mesenchymal stem cells are directly injected into the bone marrow cavity. MRL/lpr mice treated by injection of stem cells survived more than 2 years without showing symptoms of autoimmune disease. To apply this method to humans, we established a new method for bone marrow cell harvesting using cynomolgus monkeys. In this method, cells are harvested from the long bones using a perfusion method and are then injected directly into the bone marrow cavity of recipients. In this review, we show that this new method may become a powerful strategy for the treatment of various intractable diseases.