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Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning

Bhattacharya, Deepta; Rossi, Derrick J; Bryder, David LU and Weissman, Irving L (2006) In Journal of Experimental Medicine 203(1). p.73-85
Abstract
In the absence of irradiation or other cytoreductive conditioning, endogenous hematopoietic stem cells (HSCs) are thought to fill the unique niches within the bone marrow that allow maintenance of full hematopoietic potential and thus prevent productive engraftment of transplanted donor HSCs. By transplantation of purified exogenous HSCs into unconditioned congenic histocompatible strains of mice, we show that approximately 0.1-1.0% of these HSC niches are available for engraftment at any given point and find no evidence that endogenous HSCs can be displaced from the niches they occupy. We demonstrate that productive engraftment of HSCs within these empty niches is inhibited by host CD4+ T cells that recognize very subtle minor... (More)
In the absence of irradiation or other cytoreductive conditioning, endogenous hematopoietic stem cells (HSCs) are thought to fill the unique niches within the bone marrow that allow maintenance of full hematopoietic potential and thus prevent productive engraftment of transplanted donor HSCs. By transplantation of purified exogenous HSCs into unconditioned congenic histocompatible strains of mice, we show that approximately 0.1-1.0% of these HSC niches are available for engraftment at any given point and find no evidence that endogenous HSCs can be displaced from the niches they occupy. We demonstrate that productive engraftment of HSCs within these empty niches is inhibited by host CD4+ T cells that recognize very subtle minor histocompatibility differences. Strikingly, transplantation of purified HSCs into a panel of severe combined immunodeficient (SCID) mice leads to a rapid and complete rescue of lymphoid deficiencies through engraftment of these very rare niches and expansion of donor lymphoid progenitors. We further demonstrate that transient antibody-mediated depletion of CD4+ T cells allows short-term HSC engraftment and regeneration of B cells in a mouse model of B(-) non-SCID. These experiments provide a general mechanism by which transplanted HSCs can correct hematopoietic deficiencies without any host conditioning or with only highly specific and transient lymphoablation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
203
issue
1
pages
73 - 85
publisher
Rockefeller University Press
external identifiers
  • pmid:16380511
  • scopus:31344461821
ISSN
1540-9538
DOI
10.1084/jem.20051714
language
English
LU publication?
yes
id
c7b59ec3-680f-4840-8292-dea9077efa80 (old id 1136093)
date added to LUP
2008-05-16 15:54:59
date last changed
2019-07-09 03:11:09
@article{c7b59ec3-680f-4840-8292-dea9077efa80,
  abstract     = {In the absence of irradiation or other cytoreductive conditioning, endogenous hematopoietic stem cells (HSCs) are thought to fill the unique niches within the bone marrow that allow maintenance of full hematopoietic potential and thus prevent productive engraftment of transplanted donor HSCs. By transplantation of purified exogenous HSCs into unconditioned congenic histocompatible strains of mice, we show that approximately 0.1-1.0% of these HSC niches are available for engraftment at any given point and find no evidence that endogenous HSCs can be displaced from the niches they occupy. We demonstrate that productive engraftment of HSCs within these empty niches is inhibited by host CD4+ T cells that recognize very subtle minor histocompatibility differences. Strikingly, transplantation of purified HSCs into a panel of severe combined immunodeficient (SCID) mice leads to a rapid and complete rescue of lymphoid deficiencies through engraftment of these very rare niches and expansion of donor lymphoid progenitors. We further demonstrate that transient antibody-mediated depletion of CD4+ T cells allows short-term HSC engraftment and regeneration of B cells in a mouse model of B(-) non-SCID. These experiments provide a general mechanism by which transplanted HSCs can correct hematopoietic deficiencies without any host conditioning or with only highly specific and transient lymphoablation.},
  author       = {Bhattacharya, Deepta and Rossi, Derrick J and Bryder, David and Weissman, Irving L},
  issn         = {1540-9538},
  language     = {eng},
  number       = {1},
  pages        = {73--85},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning},
  url          = {http://dx.doi.org/10.1084/jem.20051714},
  volume       = {203},
  year         = {2006},
}