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MISTRG mice support engraftment and assessment of nonhuman primate hematopoietic stem and progenitor cells.

07:00 EST 24th December 2018 | BioPortfolio

Summary of "MISTRG mice support engraftment and assessment of nonhuman primate hematopoietic stem and progenitor cells."

Pre-clinical feasibility, safety, and efficacy testing of hematopoietic stem cell (HSC)-mediated gene therapy approaches is commonly performed in large animal models such as nonhuman primates (NHPs). Here we wished to determine whether mouse models would allow engraftment of NHP HSPCs which would enable more facile and less costly evaluation of promising strategies. In this study, we comprehensively tested two mouse strains for the engraftment of NHP CD34 hematopoietic stem and progenitor cells. No engraftment of NHP HSPCs was observed in NSG mice, whereas the humanized MISTRG model did demonstrate dose-dependent multilineage engraftment of NHP cells in the peripheral blood, bone marrow, spleen, and thymus. Most importantly and closely mimicking the hematopoietic recovery of autologous stem cell transplants in the NHP, only HSC-enriched CD34CD90CD45RA cell fractions did engraft and reconstituted the bone marrow stem cell niche in MISTRG mice. In summary, we here report the first "monkeynized" mouse xenograft model that closely recapitulates the autologous hematopoietic reconstitution in the NHP stem and progenitor cell transplantation and gene therapy model. Availability of this model has the potential to pre-evaluate novel HSC-mediated gene therapy approaches, inform studies in the NHP, and improve the overall outcome of large-animal experiments.

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This article was published in the following journal.

Name: Experimental hematology
ISSN: 1873-2399
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