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Chimerism and gene therapy - lessons learned from non-conditioned murine bone marrow transplantation models
Jazbec Gradišar, Katerina, 1981- ...
Objective Hematopoietic stem and progenitor cells (HSPCs) can be used as a vector for gene therapies. In order to predict the number of HSPCs cells necessary to achieve the target level of chimerism ...in an autologous setting, syngeneic male bone marrow (BM) cells were transplanted into 35 non-conditioned female BALB/c mice. Method The resulting chimerism was determined at 6-53 weeks by using qPCR, cell subpopulation sorting, and colony-forming units (CFU) analysis. Results After the transplantation of 125.8 +- 2.5 million nucleated BM cells, the BM of recipients contained 20.0% +- 2.8% donor cells, representing a chimerism of 0.16% +- 0.02% per one million transplanted nucleated BM cells. Chimerism levels in the BM, neutrophils, and B cells were comparable, whereas in T cells it was lower, and in CFU was approximately twice greater than in BM. Conclusion By extrapolating our murine data, and data from some previous studies to a human non-conditioned autologous CD34+ HSPC transplantation setting, we conclude that approximately 44 million CD34+ HSPCs would be needed to achieve 20% donor chimerism in a 70 kg human, which could serve as a starting point for the future use of HSCPs in gene and cell therapy.
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