Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA.
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA; Allen Discovery Center, Tufts University, 200 College Avenue, Medford, MA, 02155, USA.
Biochem Biophys Res Commun. 2020 Sep 10;530(1):240-245. doi: 10.1016/j.bbrc.2020.06.149. Epub 2020 Aug 4.
Historically, the field of tissue engineering has been adept at modulating the chemical and physical microenvironment. This approach has yielded significant progress, but it is imperative to further integrate our understanding of other fundamental cell signaling paradigms into tissue engineering methods. Bioelectric signaling has been demonstrated to be a vital part of tissue development, regeneration, and function across organ systems and the extracellular matrix is known to alter the bioelectric properties of cells. Thus, there is a need to bolster our understanding of how matrix and bioelectric signals interact to drive cell phenotype. We examine how cardiac progenitor cell differentiation is altered by simultaneous changes in both resting membrane potential and extracellular matrix composition. Pediatric c-kit cardiac progenitor cells were differentiated on fetal or adult cardiac extracellular matrix while being treated with drugs that alter resting membrane potential. Smooth muscle gene expression was increased with depolarization and decreased with hyperpolarization while endothelial and cardiac expression were unchanged. Early smooth muscle protein expression is modified by matrix developmental age, with fetal ECM appearing to amplify the effects of resting membrane potential. Thus, combining matrix composition and bioelectric signaling represents a potential alternative for guiding cell behavior in tissue engineering and regenerative medicine.
从历史上看，组织工程领域擅长调节化学和物理微环境。这种方法已经取得了重大进展，但必须进一步将我们对其他基本细胞信号转导范例的理解纳入组织工程方法中。生物电信号已被证明是器官系统中组织发育、再生和功能的重要组成部分，细胞外基质已知会改变细胞的生物电特性。因此，需要加强我们对基质和生物电信号如何相互作用以驱动细胞表型的理解。我们研究了在静息膜电位和细胞外基质组成同时发生变化的情况下，心脏祖细胞分化如何发生改变。儿科 c-kit 心脏祖细胞在胎儿或成人心脏细胞外基质上分化，同时用改变静息膜电位的药物处理。去极化增加平滑肌基因表达，超极化减少平滑肌基因表达，而内皮和平滑肌表达不变。早期平滑肌蛋白表达受基质发育年龄的修饰，胎儿 ECM 似乎放大了静息膜电位的作用。因此，结合基质组成和生物电信号代表了在组织工程和再生医学中指导细胞行为的一种潜在替代方法。
