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E4 enhances human HSPC engraftment in NSG mice
through regeneration of the MSC compartment of the BM niche after irradiation, or a combined effect on human HSPC (Figures 2 and 3) and niche cells (Figure 6). We can, therefore, hypothesize that estrogens might coordinate HSPC proliferation and recovery of the BM niche in the context of HSC transplantation.
We suggest that the results reported could have some significant clinical implications. E4 has a safer therapeu- tic window than E2, which facilitates its clinical use.16 Additionally, E4 has been tested in several clinical trials and its safety and efficacy have been determined in dif- ferent conditions, such as contraception,40 menopause,41 osteoporosis42 and breast cancer.43 The clinical applica- tion of E4 to modulate HSPC could, therefore, be consid- ered for improving HSPC transplantation in the near future. The clinical use of E4 might potentially facilitate the transplantation of single cord blood units, the autol- ogous transplantation of genetically modified HSPC to treat inherited hematopoietic diseases or in any situation in which a limited number of HSPC has to be infused. The administration of a clinically approved estrogen, such as E4, after HSPC transplantation could lead to an improvement in overall hematopoietic engraftment in the recipient.
Disclosures
JAB and JCS are consultants for Rocket Pharmaceuticals (NY,
USA). The other authors declare that they have no conflicts of interest to disclose.
Contribution
JCS and OQB conceived and designed the experiments. SFB, IO, FBA, SBM, JGM, MDR, RS, OA and OQB conducted the experiments. RY, YFS, DA and AZ provided reagents. AZ and JAB contributed with ideas. SFB, JCS and OQB wrote the man- uscript.
Acknowledgments
The authors would like to thank Miguel A. Martin for the careful maintenance of NSG mice, and Norman Feltz for review- ing the manuscript.
Funding
This work was supported by grants from “Ministerio de Economía, Comercio y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER)” (SAF2017-84248-P), “Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III” (RD16/0011/0011), TERCEL (“Red de Terapia Celular” of the “Instituto de Salud Carlos III”) and AvanCell consortium of “Comunidad de Madrid”. The authors also thank Fundación Botín for promoting translational research at the Hematopoietic Innovative Therapies Division of the CIEMAT. CIBERER is an initiative of the “Instituto de Salud Carlos III” and “Fondo Europeo de Desarrollo Regional (FEDER)”.
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