Bone marrow stromal cells from β -thalassemia patients have impaired hematopoietic supportive capacity

摘要: BACKGROUND. The human bone marrow (BM) niche contains a population of mesenchymal stromal cells (MSCs) that provide physical support and regulate hematopoietic stem cell (HSC) homeostasis. β-Thalassemia (BT) is hereditary disorder characterized by altered hemoglobin beta-chain synthesis amenable to allogeneic HSC transplantation gene therapy. Iron overload (IO) common complication in BT patients affecting several organs. However, data on the BM compartment are scarce. METHODS. MSCs were isolated from aspirates healthy donors (HDs) patients. state IO was assessed correlated with presence primitive vitro vivo. Hematopoietic supportive capacity evaluated transwell migration assay 2D coculture CD34+ HSCs. In vivo, ability facilitate engraftment tested xenogenic transplant model, whereas sustain hematopoiesis humanized ossicle models. RESULTS. We report that, despite iron chelation, high levels ferritin, indicative accumulation niche. found pauperization most MSC pool caused increased ROS production which impaired stemness properties. confirmed reduced frequency vivo also discovered weakened antioxidative response diminished expression niche–associated genes BT-MSCs. This functional impairment cotransplantation models. addition, BT-MSCs failed form proper models. CONCLUSION. Our results suggest an highlight need for novel strategies target reduce oxidative stress before transplantation. FUNDING. work supported SR-TIGET Core grant Fondazione Telethon Ricerca Corrente.