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Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors

Bhattacharya, D ; Bryder, David LU ; Rossi, DJ and Weissman, IL (2006) In Cell Cycle 5(11). p.1135-1139
Abstract
The replacement of abnormal hematopoietic stem cells (HSCs) with normal transplanted HSCs can correct a wide range of hematologic disorders. Here, we provide evidence that transplantation of more differentiated progenitor cells can be used to more rapidly correct lymphoid deficiencies in unconditioned immunocompromised mice. Transplantation of flk2+ multipotent progenitors led to robust B and T cell reconstitution that was maintained for at least 16 weeks. Antigenic challenge at 16 weeks post-transplantation revealed that reconstituted lymphocytes maintained a functional repertoire. In contrast to the persistent lymphocytic engraftment, myeloid chimerism was lost by 12 weeks post-transplantation consistent with the fact that flk2+... (More)
The replacement of abnormal hematopoietic stem cells (HSCs) with normal transplanted HSCs can correct a wide range of hematologic disorders. Here, we provide evidence that transplantation of more differentiated progenitor cells can be used to more rapidly correct lymphoid deficiencies in unconditioned immunocompromised mice. Transplantation of flk2+ multipotent progenitors led to robust B and T cell reconstitution that was maintained for at least 16 weeks. Antigenic challenge at 16 weeks post-transplantation revealed that reconstituted lymphocytes maintained a functional repertoire. In contrast to the persistent lymphocytic engraftment, myeloid chimerism was lost by 12 weeks post-transplantation consistent with the fact that flk2+ progenitors are non-self-renewing. Thus, while more differentiated progenitors are capable of rescuing lymphoid deficiencies, transplantation of HSCs must be used for the correction of non-lymphoid disorders, and, we propose, very long-term immune reconstitution. Based on recent evidence, we discuss novel strategies to achieve the replacement of abnormal HSCs without the use of cytotoxic conditioning regimens. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
transplantation, immuno-deficient, stem cell niche, non-myeloablative, stem cells
in
Cell Cycle
volume
5
issue
11
pages
1135 - 1139
publisher
Landes Bioscience
external identifiers
  • pmid:16760650
  • wos:000238581100003
  • scopus:33744938164
ISSN
1551-4005
language
English
LU publication?
yes
id
f37b7224-890b-4518-9382-860e1d7e8cce (old id 405694)
alternative location
http://www.landesbioscience.com/journals/cc/abstract.php?id=2772
date added to LUP
2016-04-01 11:35:11
date last changed
2020-12-27 06:12:02
@article{f37b7224-890b-4518-9382-860e1d7e8cce,
  abstract     = {The replacement of abnormal hematopoietic stem cells (HSCs) with normal transplanted HSCs can correct a wide range of hematologic disorders. Here, we provide evidence that transplantation of more differentiated progenitor cells can be used to more rapidly correct lymphoid deficiencies in unconditioned immunocompromised mice. Transplantation of flk2+ multipotent progenitors led to robust B and T cell reconstitution that was maintained for at least 16 weeks. Antigenic challenge at 16 weeks post-transplantation revealed that reconstituted lymphocytes maintained a functional repertoire. In contrast to the persistent lymphocytic engraftment, myeloid chimerism was lost by 12 weeks post-transplantation consistent with the fact that flk2+ progenitors are non-self-renewing. Thus, while more differentiated progenitors are capable of rescuing lymphoid deficiencies, transplantation of HSCs must be used for the correction of non-lymphoid disorders, and, we propose, very long-term immune reconstitution. Based on recent evidence, we discuss novel strategies to achieve the replacement of abnormal HSCs without the use of cytotoxic conditioning regimens.},
  author       = {Bhattacharya, D and Bryder, David and Rossi, DJ and Weissman, IL},
  issn         = {1551-4005},
  language     = {eng},
  number       = {11},
  pages        = {1135--1139},
  publisher    = {Landes Bioscience},
  series       = {Cell Cycle},
  title        = {Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors},
  url          = {http://www.landesbioscience.com/journals/cc/abstract.php?id=2772},
  volume       = {5},
  year         = {2006},
}