Human intestinal transplantation often results in long-term mixed chimerism of donor and recipient blood in transplant patients. CCTI researchers followed the phenotypes of chimeric peripheral blood cells in 21 patients receiving intestinal allografts over 5 years. Donor lymphocyte phenotypes suggested a contribution of hematopoietic stem and progenitor cells (HSPCs) from the graft. Surprisingly, they detected donor-derived HSPCs in intestinal mucosa, Peyer’s patches, mesenteric lymph nodes, and liver. Human gut HSPCs are phenotypically similar to bone marrow HSPCs and have multilineage differentiation potential in vitro and in vivo. Analysis of circulating post-transplant donor T cells suggests that they undergo selection in recipient lymphoid organs to acquire immune tolerance. This longitudinal study of human HSPCs carried in intestinal allografts demonstrates their turnover kinetics and gradual replacement of donor-derived HSPCs from a circulating pool. Thus, our scientists have demonstrated the existence of functioning HSPCs in human intestines with implications for promoting tolerance in transplant recipients. Find the full paper in the latest issue of Cell Stem Cell here.