Targeting stem cell niche can protect hematopoietic stem cells from chemotherapy and G-CSF treatment

摘要

Introduction Hematopoietic stem/progenitor cells (HSPCs) reside in a tightly controlled local microenvironment called bone marrow niche. The specialized microenvironment or niche not only provides a favorable habitat for HSPC maintenance and development but also governs stem cell function. Method We investigated the effect of cytotoxic drugs on bone marrow niche. To mimic the multiple rounds of chemotherapy followed by autologous hematopoietic stem cells (HSCs) transplantation in a clinical setting, we further verified the hypothesis that targeting the niche might improve stem cell–based therapies in mouse models. Results We found that multiple rounds of cytotoxic drug treatment significantly disrupted niche and serum osteocalcin level was significantly reduced after treatment in autologous HSPCs transplanted patients (P = 0.01). In mouse models, the number of CD45 ? Ter119 ? OPN + osteoblasts was significantly reduced after multiple rounds of chemotherapies and granulocyte colony stimulating factor (G-CSF) treatment (P Conclusion These data provide new evidence that the niche may be an important target for drug-based stem cell therapy.