Stem cell engraftment within our G(P)RASP

摘要

In this issue of Blood, Morales-Herna ' ndez et al describe an essential role for G protein-coupled receptor-associated sorting proteins (GPRASP) in regulating hematopoietic stem cell (HSC) survival, proliferation, and in vivo engraftment capacity, findings with potentially significant implications for the current practice of hematopoietic cell transplantation.(1) Hematopoietic cell transplantation provides curative therapy for thousands of patients with hematologic malignancies, bone marrow (BM) failure, and other life-threatening hematologic disorders.(2) However, many patients who meet criteria to benefit from hematopoietic cell transplantation lack an HLA-matched related or unrelated donor,(3) and alternative donor transplantation, utilizing haploidentical related donors or cord blood, presents challenges related to relapse rate and graft failure risk, respectively.(4,5) Exciting advances in HSC gene editing and gene transfer have reignited clinical gene therapy trials for hematologic and immune deficiency diseases, but ex vivo genetic manipulation of HSCs can diminish HSC engraftment capacity in vivo.(6) The development of techniques to enhance the repopulating capacity of donor HSCs could have broad impact in hematopoietic cell transplantation and gene therapy. However, the development of translatable methods to enhance human HSC engraftment has been impeded by a lack of understanding of the mechanisms that control HSC engraftment following transplantation. In this issue of Blood, Morales-Hernandez et al describe the fascinating role of GPRASPs in regulating HSC repopulating capacity following transplantation.