New Strategy of Acute Graft-vs-Host Disease: Investigation of a Reduced Dose of Antithymocyte Globulin in Haploidentical Hematopoietic Stem Cell Transplantation

Sun, Ying; Wei, Catherine; Cao, Chun; Tan, Xu; Zeng, Hanqing; Luo, Yun; Chen, L.

doi:10.1016/j.transproceed.2018.10.028

Cited by 1 publication

(1 citation statement)

References 27 publications

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“…Transplanted HSCs must reach and seed specific niches in recipient bone marrow (BM), a process termed "homing and engraftment." 1 Although recent advances in HSCT, such as milder conditioning regimens and haplotransplantation, have improved on recognized limitations of HSCT, including donor availability and conditioning-related morbidities, [2][3][4][5][6] more could be done to improve the safety, efficacy, and accessibility of this critical therapy. For example, ex vivo manipulation of HSCs for gene therapy compromises their homing and engraftment, [7][8][9][10] small cell numbers limit the utility of cord blood HSCs as a source for transplantation, [11][12][13][14][15][16] and underrepresentation of minorities on national bone marrow registries contributes significantly to limited donor access for these groups.…”

Section: Introductionmentioning

confidence: 99%

GPRASP proteins are critical negative regulators of hematopoietic stem cell transplantation

Morales-Hernández

Benaksas

Chabot

et al. 2020

Blood

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Hematopoietic stem cell transplantation (HSCT) is often exploited to treat hematologic disease. Donor HSCs must survive, proliferate and differentiate in the damaged environment of the reconstituting niche. Illuminating molecular mechanisms regulating the activity of transplanted HSCs will inform efforts to improve HSCT. Here, we report that GPRASP proteins function as negative regulators of HSCT. Silencing of Gprasp1 or Gprasp2 increased the survival, quiescence, migration, niche retention and hematopoietic repopulating activity of hematopoietic stem and progenitor cells (HSPCs) post-transplant. We further show that GPRASP1 and GPRASP2 promote the degradation of CXCR4, a master regulator of HSC function during transplantation. CXCR4 accumulates in Gprasp-deficient HSPCs, boosting their function post-transplant. Thus, GPRASPs negatively regulate CXCR4 stability in HSCs. Our work reveals GPRASP proteins as negative regulators of HSCT and CXCR4 activity. Disruption of GPRASP/CXCR4 interactions could be exploited in the future to enhance the efficiency of HSCT.

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