在一項(xiàng)新的研究中,加州大學(xué)洛杉磯分校研究人員發(fā)現(xiàn)用于在體外培養(yǎng)心肌細(xì)胞的物理基質(zhì)(physical matrix)的彈性可能是心臟組織工程取得成功的關(guān)鍵.相關(guān)研究結(jié)果于2013年3月21日在線發(fā)表在Science and Technology of Advanced Materials期刊上,論文標(biāo)題為"Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells".
成年人心肌是人體內(nèi)最為不容易再生的組織.但是胚胎心肌細(xì)胞(embryonic cardiomyocyte)能夠增殖,而且胚胎干細(xì)胞(embryonic stem cells, ESCs)能夠被用來(lái)無(wú)限制地產(chǎn)生新的心臟組織.
在這項(xiàng)新的研究中,加州大學(xué)洛杉磯分校研究人員發(fā)現(xiàn)用于在體外培養(yǎng)心肌細(xì)胞的物理基質(zhì)可能是心臟組織工程研究取得成功的關(guān)鍵.他們發(fā)現(xiàn)堅(jiān)硬的基質(zhì)不僅能夠改善現(xiàn)存的心肌細(xì)胞功能(就像科學(xué)家們之前發(fā)現(xiàn)的那樣),而且也促進(jìn)胚胎干細(xì)胞產(chǎn)生心肌細(xì)胞.因此,操縱用來(lái)培養(yǎng)干細(xì)胞的基質(zhì)的硬度可能能夠產(chǎn)生新的心肌組織.
活的生物體內(nèi)存在著一種被稱(chēng)作間充質(zhì)干細(xì)胞(mesenchymal stem cells, MSCs)的成體干細(xì)胞.當(dāng)在體外培養(yǎng)時(shí),這種成體干細(xì)胞對(duì)不同基質(zhì)材料的彈性極其敏感.比如,柔軟的模擬大腦組織的培養(yǎng)基質(zhì)促進(jìn)MSCs分化為神經(jīng)元,而類(lèi)似于骨組織的堅(jiān)硬基質(zhì)促進(jìn)MSCs分化為骨細(xì)胞.
在這項(xiàng)研究中,研究人員利用基于硅膠的硬度可發(fā)生變化的有機(jī)聚合物基質(zhì)來(lái)培養(yǎng)小鼠ESCs和人ESCs,并研究了基質(zhì)彈性在心肌發(fā)育中的作用.他們發(fā)現(xiàn)剛硬的基質(zhì)促進(jìn)ESCs產(chǎn)生更多的心肌細(xì)胞.此外,當(dāng)起源自ESCs的心肌細(xì)胞與從發(fā)育中的胚胎內(nèi)收集的心肌細(xì)胞一起培養(yǎng)時(shí),它們?cè)诠δ苌铣墒?并且發(fā)生同步跳動(dòng).
研究人員建議進(jìn)一步研究生物物理信號(hào)如何決定著ESCs的命運(yùn),以便改進(jìn)用于再生醫(yī)學(xué)的心臟組織培養(yǎng)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.
