Sundelacruz Sarah, Levin Michael, Kaplan David L
Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
PLoS One. 2008;3(11):e3737. doi: 10.1371/journal.pone.0003737. Epub 2008 Nov 17.
Control of stem cell behavior is a crucial aspect of developmental biology and regenerative medicine. While the functional role of electrophysiology in stem cell biology is poorly understood, it has become clear that endogenous ion flows represent a powerful set of signals by means of which cell proliferation, differentiation, and migration can be controlled in regeneration and embryonic morphogenesis.
METHODOLOGY/PRINCIPAL FINDINGS: We examined the membrane potential (V(mem)) changes exhibited by human mesenchymal stem cells (hMSCs) undergoing adipogenic (AD) and osteogenic (OS) differentiation, and uncovered a characteristic hyperpolarization of differentiated cells versus undifferentiated cells. Reversal of the progressive polarization via pharmacological modulation of transmembrane potential revealed that depolarization of hMSCs prevents differentiation. In contrast, treatment with hyperpolarizing reagents upregulated osteogenic markers.
CONCLUSIONS/SIGNIFICANCE: Taken together, these data suggest that the endogenous hyperpolarization is a functional determinant of hMSC differentiation and is a tractable control point for modulating stem cell function.
干细胞行为的控制是发育生物学和再生医学的关键方面。虽然电生理学在干细胞生物学中的功能作用了解甚少，但很明显，内源性离子流代表了一组强大的信号，通过这些信号可以在再生和胚胎形态发生过程中控制细胞增殖、分化和迁移。
方法/主要发现：我们检测了人骨髓间充质干细胞（hMSCs）在成脂（AD）和成骨（OS）分化过程中表现出的膜电位（V(mem)）变化，发现分化细胞相对于未分化细胞存在特征性超极化。通过跨膜电位的药理学调节逆转渐进性极化表明，hMSCs的去极化可阻止分化。相反，用超极化试剂处理可上调成骨标志物。
结论/意义：综上所述，这些数据表明内源性超极化是hMSC分化的功能决定因素，是调节干细胞功能的一个可控控制点。
