Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool

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 ShenAdam Griesemer, Donna L. Farber, Tomoaki Kato, Megan Sykes

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish
Pages (from-to)227-239.e8
JournalCell Stem Cell
Volume24
Issue number2
DOIs
StatePublished - 7 Feb 2019

Keywords

  • T cell receptor
  • circulating pool
  • hematopoietic progenitor cell
  • hematopoietic stem cell
  • immune tolerance
  • intestinal allograft
  • intestinal transplantation
  • mixed chimerism
  • recent thymic immigrants
  • recipient repopulation

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