NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning.
Scidhematopoietic 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, NODscidmice 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 NODscidgamma (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.
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK. tom.verbiest@oncology.ox.ac.uk.|CRUK & MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. tom.verbiest@oncology.ox.ac.uk.
Tom
T
Verbiest
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK. rosemary.finnon@phe.gov.uk.
Rosemary
R
Finnon
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK. natalie.brown@phe.gov.uk.
Natalie
N
Brown
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK. paul.finnon@phe.gov.uk.
Paul
P
Finnon
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK. simon.bouffler@phe.gov.uk.
Simon
S
Bouffler
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK. christophe.badie@phe.gov.uk.
Christophe
C
Badie
D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression; D017930:Genes, Reporter; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000528:radiation effects; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D055153:Stem Cell Niche / Q000276:immunology / Q000528:radiation effects*; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous; D014965:X-Rays; D000097573:Red Fluorescent Protein
D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
NOD scid gamma (NSG); engraftment; hematopoietic niche occupancy defect; hematopoietic stem cells; transplantation