在一项新的研究中,加州大学洛杉矶分校研究人员发现用于在体外培养心肌细胞的物理基质(physical matrix)的弹性可能是心脏组织工程取得成功的关键.相关研究结果于2013年3月21日在线发表在Science and Technology of Advanced Materials期刊上,论文标题为"Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells".
成年人心肌是人体内最为不容易再生的组织.但是胚胎心肌细胞(embryonic cardiomyocyte)能够增殖,而且胚胎干细胞(embryonic stem cells, ESCs)能够被用来无限制地产生新的心脏组织.
在这项新的研究中,加州大学洛杉矶分校研究人员发现用于在体外培养心肌细胞的物理基质可能是心脏组织工程研究取得成功的关键.他们发现坚硬的基质不仅能够改善现存的心肌细胞功能(就像科学家们之前发现的那样),而且也促进胚胎干细胞产生心肌细胞.因此,操纵用来培养干细胞的基质的硬度可能能够产生新的心肌组织.
活的生物体内存在着一种被称作间充质干细胞(mesenchymal stem cells, MSCs)的成体干细胞.当在体外培养时,这种成体干细胞对不同基质材料的弹性极其敏感.比如,柔软的模拟大脑组织的培养基质促进MSCs分化为神经元,而类似于骨组织的坚硬基质促进MSCs分化为骨细胞.
在这项研究中,研究人员利用基于硅胶的硬度可发生变化的有机聚合物基质来培养小鼠ESCs和人ESCs,并研究了基质弹性在心肌发育中的作用.他们发现刚硬的基质促进ESCs产生更多的心肌细胞.此外,当起源自ESCs的心肌细胞与从发育中的胚胎内收集的心肌细胞一起培养时,它们在功能上成熟,并且发生同步跳动.
研究人员建议进一步研究生物物理信号如何决定着ESCs的命运,以便改进用于再生医学的心脏组织培养方法.（生物谷Bioon.com）
doi:10.1088/1468-6996/14/2/025003
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Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells
Armin Arshi1, Yasuhiro Nakashima1, Haruko Nakano1,2, Sarayoot Eaimkhong3,4, Denis Evseenko5,6,7, Jason Reed4, Adam Z Stieg4,8, James K Gimzewski3,4,6,8 and Atsushi Nakano1,2,6,7,9
While adult heart muscle is the least regenerative of tissues, embryonic cardiomyocytes are proliferative, with embryonic stem (ES) cells providing an endless reservoir. In addition to secreted factors and cell–cell interactions, the extracellular microenvironment has been shown to play an important role in stem cell lineage specification, and understanding how scaffold elasticity influences cardiac differentiation is crucial to cardiac tissue engineering. Though previous studies have analyzed the role of matrix elasticity on the function of differentiated cardiomyocytes, whether it affects the induction of cardiomyocytes from pluripotent stem cells is poorly understood. Here, we examine the role of matrix rigidity on cardiac differentiation using mouse and human ES cells. Culture on polydimethylsiloxane (PDMS) substrates of varied monomer-to-crosslinker ratios revealed that rigid extracellular matrices promote a higher yield of de novo cardiomyocytes from undifferentiated ES cells. Using a genetically modified ES system that allows us to purify differentiated cardiomyocytes by drug selection, we demonstrate that rigid environments induce higher cardiac troponin T expression, beating rate of foci, and expression ratio of adult α- to fetal β- myosin heavy chain in a purified cardiac population. M-mode and mechanical interferometry image analyses demonstrate that these ES-derived cardiomyocytes display functional maturity and synchronization of beating when co-cultured with neonatal cardiomyocytes harvested from a developing embryo. Together, these data identify matrix stiffness as an independent factor that instructs not only the maturation of already differentiated cardiomyocytes but also the induction and proliferation of cardiomyocytes from undifferentiated progenitors. Manipulation of the stiffness will help direct the production of functional cardiomyocytes en masse from stem cells for regenerative medicine purposes.
