Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool.
Animals
Cell Differentiation
Cell Line
Cell Lineage
Cell Movement
Chimerism
Graft vs Host Disease
/ immunology
Hematopoietic Stem Cells
/ cytology
Humans
Immune Tolerance
Intestinal Mucosa
/ cytology
Intestines
/ cytology
Liver
/ cytology
Lymph Nodes
/ cytology
Mice
Peyer's Patches
/ cytology
Phenotype
T-Lymphocytes
/ cytology
Tissue Donors
Transplantation, Homologous
T cell receptor
circulating pool
hematopoietic progenitor cell
hematopoietic stem cell
immune tolerance
intestinal allograft
intestinal transplantation
mixed chimerism
recent thymic immigrants
recipient repopulation
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
07 02 2019
07 02 2019
Historique:
received:
09
03
2018
revised:
20
07
2018
accepted:
02
11
2018
pubmed:
7
12
2018
medline:
28
3
2020
entrez:
4
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30503142
pii: S1934-5909(18)30543-5
doi: 10.1016/j.stem.2018.11.007
pmc: PMC6398344
mid: NIHMS1511883
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
227-239.e8Subventions
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106711
Pays : United States
Organisme : NIH HHS
ID : S10 OD020056
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106697
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007367
Pays : United States
Organisme : NIH HHS
ID : S10 OD023547
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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