Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency

摘要

Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not onlyudto biochemical but also to physical cues, such as substrate topography and stiffness. To simulate theuddynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogateudsubstrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity canudbe adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown onudour hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrateudelasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergoudadipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover,udwe demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90%udwithout any loss of multiple lineage potential by changing the substrate elasticity every 2nd days.udSuch “dynamic in vitro niche” can be used not only for a better understanding of the role of dynamicudmechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stemudcells to a specific lineage.