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 @entity19 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 @entity1 (P = 0.01). In @entity19 models, the number of @entity8236 (-)Ter119(-)OPN(+) osteoblasts was significantly reduced after multiple rounds of chemotherapies and @entity24778 ( @entity24778 ) treatment (P < 0.01). @entity10173 ( @entity10173 ) or @entity5271 ( @entity5271 ) treatment significantly increased the number of HSCs mobilized into peripheral blood (PB) for stem cell harvesting and protected stem cells from repeated exposure to cytotoxic chemotherapy. Treatments with @entity24778 and @entity10173 significantly increased the preservation of the HSC pool (P < 0.05). Moreover, recipient @entity19 transplanted with circulation HSPCs that were previously treated with @entity10173 and @entity5271 showed robust myeloid and lymphatic cell engraftment compared to the @entity19 transplanted with HSCs after chemotherapy or @entity24778 treatment. CONCLUSION: These data provide new evidence that the niche may be an important target for drug-based stem cell therapy.

Targeting stem cell niche can protect hematopoietic stem cells from chemotherapy and XXXX treatment.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity8236 :: ('19264(Tax:10090)', 'Gene') :: ['CD45'] @entity10173 :: ('19226(Tax:10090)', 'Gene') :: ['Parathyroid hormone', 'PTH'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity24778 :: ('12985(Tax:10090)', 'Gene') :: ['G-CSF', 'granulocyte colony stimulating factor'] @entity5271 :: ('21943(Tax:10090)', 'Gene') :: ['receptor activator of nuclear factor kappa-B ligand', 'RANKL']
@entity24778 :: (12985(Tax:10090),Gene) :: ['G-CSF']
