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NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning

Scid hematopoietic stem cells (HSCs) have an intrinsic defect in their maintenance within the bone marrow (BM) niche which facilitates HSC transplantation without the absolute requirement of prior conditioning. Nevertheless, NOD scid mice have a significantly altered life span due to early developme...

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Autores principales: Verbiest, Tom, Finnon, Rosemary, Brown, Natalie, Finnon, Paul, Bouffler, Simon, Badie, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133850/
https://www.ncbi.nlm.nih.gov/pubmed/27827995
http://dx.doi.org/10.3390/ijms17111850
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author Verbiest, Tom
Finnon, Rosemary
Brown, Natalie
Finnon, Paul
Bouffler, Simon
Badie, Christophe
author_facet Verbiest, Tom
Finnon, Rosemary
Brown, Natalie
Finnon, Paul
Bouffler, Simon
Badie, Christophe
author_sort Verbiest, Tom
collection PubMed
description Scid hematopoietic stem cells (HSCs) have an intrinsic defect in their maintenance within the bone marrow (BM) niche which facilitates HSC transplantation without the absolute requirement of prior conditioning. Nevertheless, NOD scid mice have a significantly altered life span due to early development of thymic lymphomas, which compromises the ability to study the long-term fate of exogenous HSCs and their progeny. Here, we present data on the transplantation of HSCs into NOD scid gamma (NSG) mice to achieve long-term engraftment without prior conditioning. We transplanted allogeneic HSCs constitutively expressing the mCherry fluorescent marker into age-matched NSG mice and assessed donor chimerism 6 months post-transplantation. All transplanted NSG mice showed long-term myeloid and lymphoid cell chimerism. Also, in vivo irradiated HSCs showed long-term engraftment, although overall white blood cell (WBC) donor chimerism was lower compared with non-irradiated HSCs. Using this novel NSG transplantation model, we will be able to study the effects of low dose in vivo X-ray exposure on the long-term fate of HSCs, without the requirement of prior radio-ablation of the recipient, and thus leaving the recipient’s BM microenvironment uncompromised. In conclusion, we demonstrated for the first time that allogeneic HSCs from a different inbred strain can compete for niches in the BM compartment of NSG mice.
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spelling pubmed-51338502016-12-12 NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning Verbiest, Tom Finnon, Rosemary Brown, Natalie Finnon, Paul Bouffler, Simon Badie, Christophe Int J Mol Sci Article Scid hematopoietic stem cells (HSCs) have an intrinsic defect in their maintenance within the bone marrow (BM) niche which facilitates HSC transplantation without the absolute requirement of prior conditioning. Nevertheless, NOD scid mice have a significantly altered life span due to early development of thymic lymphomas, which compromises the ability to study the long-term fate of exogenous HSCs and their progeny. Here, we present data on the transplantation of HSCs into NOD scid gamma (NSG) mice to achieve long-term engraftment without prior conditioning. We transplanted allogeneic HSCs constitutively expressing the mCherry fluorescent marker into age-matched NSG mice and assessed donor chimerism 6 months post-transplantation. All transplanted NSG mice showed long-term myeloid and lymphoid cell chimerism. Also, in vivo irradiated HSCs showed long-term engraftment, although overall white blood cell (WBC) donor chimerism was lower compared with non-irradiated HSCs. Using this novel NSG transplantation model, we will be able to study the effects of low dose in vivo X-ray exposure on the long-term fate of HSCs, without the requirement of prior radio-ablation of the recipient, and thus leaving the recipient’s BM microenvironment uncompromised. In conclusion, we demonstrated for the first time that allogeneic HSCs from a different inbred strain can compete for niches in the BM compartment of NSG mice. MDPI 2016-11-07 /pmc/articles/PMC5133850/ /pubmed/27827995 http://dx.doi.org/10.3390/ijms17111850 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Verbiest, Tom
Finnon, Rosemary
Brown, Natalie
Finnon, Paul
Bouffler, Simon
Badie, Christophe
NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning
title NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning
title_full NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning
title_fullStr NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning
title_full_unstemmed NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning
title_short NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning
title_sort nod scid gamma mice are permissive to allogeneic hsc transplantation without prior conditioning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133850/
https://www.ncbi.nlm.nih.gov/pubmed/27827995
http://dx.doi.org/10.3390/ijms17111850
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