Engineering biomimetic bone marrow niche with gene modified mesenchymal stromal cells for ex vivo culture of human hematopoietic stem and progenitor cells

• Genetically modified MSCs secreting SCF, TPO, FLT3L, and IL3 support HSPC expansion without exogenous cytokines, preserving stemness and multilineage potential. • The biomimetic feeder layer reduces culture-induced stress and improves outcomes for HDR-mediated gene editing, particularly for fetal hemoglobin reactivation. • This approach offers a cost-effective alternative to traditional cytokine supplementation, potentially lowering the overall cost of HSPC gene therapy. • The engineered MSCs closely mimic the bone marrow niche, enhancing the therapeutic value of HSPCs for gene therapy applications.