@article{a0f95b0bc175463784e3502a8ef92ace,
title = "Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors",
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.",
keywords = "Immuno-deficient, Non-myeloablative, Stem cell niche, Stem cells, Transplantation",
author = "Deepta Bhattacharya and David Bryder and Rossi, {Derrick J.} and Weissman, {Irving L.}",
note = "Funding Information: ment and C. Richter for anti-body production. The hypothesis that HSCs require a fixed tissue microenvironment within the bone This work was supported by NIH grants marrow to function properly was first proposed by Schofield over 30 years ago.1The idea 5R01HL058770 and 2R01AI047457 that such a “niche” exists was based on the observations that the bone marrow, but not the (I.L.W.). D. Bhattacharya is supported by a spleen, could sustain hematopoiesis through serial transplantations. In support of the fellowship from the Cancer Research Institute, niche hypothesis, later studies showed that irradiation was required in order to facilitate D. Bryder was supported by a scholarship sustained donor bone marrow engraftment, presumably to clear endogenous HSC from from the Swedish Medical Research Council their niches.2,3 Funding Information: (STINT), and D.J. Rossi is supported by a These and other studies also suggested that HSCs have the ability to home efficiently fellowship from the Damon Runyon Cancer to these empty niches upon intravenous transplantation. Very early work provided some Foundation. Affiliations that might be perceived evidence that some HSCs might be present in the blood,4,5 but until recently the etiologic to have biased this work are as follows: (1) I.L.W. purpose of the inherent ability of HSCs to home to their specialized microenvironments was a member of the scientific advisory board through intravascular circulation was not clear. To determine whether HSCs circulate and of Amgen and owns significant Amgen stock; rehome to their niches under physiologic conditions, Wright et al turned to a parabiosis and (2) I.L.W. cofounded and consulted for model in which cross circulation between congenically distinguishable mice was rapidly Systemix; is a cofounder and director of Stem established.6 After separation, these mice maintained long-term blood chimerism, suggesting Cells, Inc.; and recently cofounded Cellerant, that functional HSC cross-engraftment had occurred during the period of parabiosis and Inc. All other authors do not have a conflict of in the absence of any radiaton or chemotherapy to open niches. Indeed, HSC chimerism was interest.{\textcopyright}2006 LANDES BIOSCIENCEdetectable directly within the bone marrow of both partners. Additionally, approximately",
year = "2006",
month = jun,
day = "1",
doi = "10.4161/cc.5.11.2772",
language = "English (US)",
volume = "5",
pages = "1135--1139",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Taylor and Francis Ltd.",
number = "11",
}