Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool
Human intestinal transplantation often results in long-term mixed chimerism of donor and recipient blood in transplant patients. We followed the phenotypes of chimeric peripheral blood cells in 21 patients receiving intestinal allografts over 5 years. Donor lymphocyte phenotypes suggested a contribu...
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Veröffentlicht in: | Cell stem cell 2019-02, Vol.24 (2), p.227-239.e8 |
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Sprache: | eng |
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Zusammenfassung: | Human intestinal transplantation often results in long-term mixed chimerism of donor and recipient blood in transplant patients. We 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, we 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. Our 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, we have demonstrated the existence of functioning HSPCs in human intestines with implications for promoting tolerance in transplant recipients.
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•Human intestine contains hematopoietic stem cells and multiple types of progenitors•Donor graft HSPCs contribute to multilineage blood chimerism in the recipient•Long-term circulating donor T cells are tolerant to the recipient but functional•Intestinal HSPCs undergo replacement by the recipient from a circulating pool
Fu et al. demonstrate the presence and multilineage differentiation potential of hematopoietic stem and progenitor cells (HSPCs) carried in human intestinal allografts. These contribute to peripheral blood mixed chimerism in the recipient. Kinetic turnover studies revealed the gradual replacement of intestinal mucosal HSPCs by a circulating pool in humans. |
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ISSN: | 1934-5909 1875-9777 |
DOI: | 10.1016/j.stem.2018.11.007 |