Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool
人类肠异体移植物包含由循环池维持的功能性造血干细胞和祖细胞
2018-11-29, Article, 10.1016/j.stem.2018.11.007more
Abstract:
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.
First Authors:
Jianing Fu
Correspondence Authors:
Megan Sykes
All Authors:
Jianing Fu,Julien Zuber,Mercedes Martinez,Brittany Shonts,Aleksandar Obradovic,Hui Wang,Sai-ping Lau,Amy Xia,Elizabeth E Waffarn,Kristjana Frangaj,Thomas M Savage,Michael T Simpson,Suxiao Yang,Xinzheng V Guo,Michelle Miron,Takashi Senda,Kortney Rogers,Adeeb Rahman,Siu-hong Ho,Yufeng Shen,Adam Griesemer,Donna L Farber,Tomoaki Kato,Megan Sykes
