Acute graft versus host disease (GVHD) is a potentially life threatening complication after allogeneic hematopoietic stem cell transplantation. The gut is one of the most frequently affected organs in GVHD. Intestinal GVHD is often resistant to current therapies for GVHD and greatly affects the nutritional status of patients. Recent advances in understanding the biology of the intestinal immune system have revealed the significance of mechanical and chemical barriers involving the intestinal mucosa and intestinal microflora in the pathophysiology of GVHD. These barriers and flora are tightly regulated by key populations such as intestinal stem cells, Paneth cells, innate lymphoid cells, and macrophages. Recent findings for these key players in the process of intestinal GVHD are reviewed in this article.

Induced pluripotent stem (iPS) cells can be generated by transiently expressing defined factors in somatic cells such as dermal fibroblasts and blood cells and culturing them in specific medium. iPS cells are expected to provide new tools for research and development of therapies for various diseases because of two important properties : 1) they can be differentiated into any type of somatic cell (pluripotency) and 2) they can be expanded infinitely (self renew). Research for the transplantation of iPS cell-derived cartilage/chondrocytes and drug discovery by iPS cell-based disease modeling are ongoing.

Anti-human T-lymphocyte immunoglobulin, rabbit (ATG, Zetbulin(®) intravenous infusion liquid), is an immunosuppressive agent that is indicated for aplastic anemia in Japan. The "prevention of graft-versus-host disease (GVHD) for allogeneic hematopoietic stem cell transplantation in adults" indication has been added to ATG in 32 countries worldwide, but has not yet been approved for GVHD prevention in Japan. The pharmacokinetics of ATG in Japanese people has not yet been assessed. In this study, to assess ATG pharmacokinetics, ATG (2 mg/kg/day from day-4 to day-1) as a pretransplant treatment was administered to six patients who had received transplantation of HLA-haploidentical stem cells. The ATG concentration was measured using an ELISA kit for rabbit IgG. The serum ATG concentration increased with administration for 4 consecutive days, peaking at a concentration of 66.0 μg/ml (±8.8 SD). Subsequently, it gradually decreased with an elimination half-life of 21.9 days (±20.4 SD) but was still detectable in serum even a few weeks after allogeneic hematopoietic stem cell transplantation. We found the pharmacokinetics of ATG in this study to be comparable to those described in previous reports from Europe.

Through their differentiation and self-renewal capabilities, hematopoietic stem cells (HSCs) supply the vast amounts of blood cells needed throughout life. The use of surface markers to purify HSCs has been promoted. After bone marrow injury, however, HSCs are activated, and the expression pattern of HSC-related antigens changes dramatically. Endothelial cell-selective adhesion molecule (ESAM), an immunoglobulin superfamily protein, was originally identified as an endothelium-specific molecule. We recently reported ESAM as a new HSC marker. In the present study, we demonstrate the monitoring of ESAM levels to provide a useful indicator of HSC activation. Expression levels of ESAM clearly mirrored shifts in HSC status between quiescence and activation, and the shifts were more prominent than those of other HSC-related antigens. ESAMHi HSCs were active in the cell cycle while maintaining a high capacity for long-term reconstitution. More than 80% of ESAMHi HSCs were located near endothelium in the bone marrow after 5-FU treatment. Furthermore, ESAM is functionally important for HSCs to re-establish homeostatic hematopoiesis. Our data demonstrate ESAM expression levels to be useful for monitoring HSC status, tracing the proliferation of HSCs in vivo and understanding the molecular events underlying HSC activation.