Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/405694
- author
- Bhattacharya, D ; Bryder, David LU ; Rossi, DJ and Weissman, IL
- organization
- publishing date
- 2006
- 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
- 2022-04-20 18:57:26
@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}}, keywords = {{transplantation; immuno-deficient; stem cell niche; non-myeloablative; stem cells}}, 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}}, }