Irradiated mesenchymal stem cells improve the ex vivo expansion of hematopoietic progenitors by partly mimicking the bone marrow endosteal environment

摘要: Abstract Mesenchymal Stem Cells (MSCs) regulate the growth and differentiation of Hematopoietic Progenitor cells (HPCs) through release soluble factors or their into osteoblasts. We recently demonstrated that expansion megakaryocyte (MK) progenitors ex vivo had reached a plateau when CD34+ were grown with two optimized cytokine cocktails developed for MK. Hence, we sought to determine whether co-culture Bone Marrow (BM) MSCs could further increase myeloid MK progenitors. First, tested impact cell–cell contact pre-irradiation treatment identify condition best supports HPC expansion. This screen revealed expansions generally greater in non-contact conditions, appeared be added benefits. Improved both irradiated without was subsequently confirmed. Next, array profiling carried out investigate why irradiation promoted progenitor levels as many 33 potentially altered. ELISA confirmed significant up regulation NT-3 IGFBP-2. Since, these are known released by important osteogenic endothelial cells, investigated induced rapid osteogenic-like but not endothelial-like cells. Supporting this finding, increased MSCs-derived Altogether, results indicate improved HPCs obtained is due part osteoblast-like thereby recreating an endosteal-like environment provides support