制造逐階段組織發(fā)育模擬基質(zhì)材料,，它們模擬間充質(zhì)干細(xì)胞成骨分化和成脂分化期間的胞外基質(zhì)。

日本國立材料科學(xué)研究所國際材料納米建筑學(xué)研究中心組織再生材料部門成功地開發(fā)一種能夠控制干細(xì)胞分化以便應(yīng)用于再生醫(yī)學(xué)的基質(zhì)材料,。2011年12月15日,，這些研究結(jié)果在線發(fā)表《生物材料》(Biomaterials)期刊上。

要使得再生醫(yī)學(xué)成為現(xiàn)實,，人們必須能夠誘導(dǎo)干細(xì)胞分化為特定細(xì)胞類型以便重建所需要的組織或器官來治療疾病或缺陷,?？刂聘杉?xì)胞分化的技術(shù)是這一過程最為關(guān)鍵的方面。如今,，人們正在關(guān)注胞外基質(zhì)(extracellular matrix)——它在體內(nèi)包圍干細(xì)胞---在影響干細(xì)胞分化中的作用,。然而,，因為包圍分化細(xì)胞(differentiating cell)的胞外基質(zhì)是非常復(fù)雜的,，而且根據(jù)分化的階段它還會發(fā)生結(jié)構(gòu)重塑，所以要模仿這種在不同階段結(jié)構(gòu)發(fā)生變化的基質(zhì)制造出胞外基質(zhì)材料一直是非常困難的,。

在這篇研究中,，研究小組成功地制造出兩種類型的基質(zhì)材料，它們都能模仿干細(xì)胞分化期間發(fā)生動態(tài)變化的胞外基質(zhì),。它們是“逐階段骨生成模仿基質(zhì)(stepwise osteogenesis-mimicking matrix)”和“逐階段脂肪生成模仿基質(zhì)(stepwise adipogenesis-mimicking matrix)”,，它們分別模仿間充質(zhì)干細(xì)胞分化為成骨細(xì)胞(osteoblast)和脂肪細(xì)胞時的胞外基質(zhì)。

使用這兩種“逐階段組織發(fā)育模仿基質(zhì)(stepwise tissue development-mimicking matrix)”,，研究人員成功地控制間充質(zhì)干細(xì)胞的成骨分化和成脂分化,。這些結(jié)果表明胞外基質(zhì)在控制間充質(zhì)干細(xì)胞的成骨發(fā)生和成脂發(fā)生平衡中發(fā)揮著重要的作用。

在未來,，研究人員期待這種逐階段組織發(fā)育模仿基質(zhì)在闡釋胞外基質(zhì)在用于再生醫(yī)學(xué)的誘導(dǎo)性多功能細(xì)胞,、胚胎干細(xì)胞和其他干細(xì)胞分化時所發(fā)揮功能的研究中也起著一種關(guān)鍵性作用?；诠琴|(zhì)疏松癥可能是成骨分化和成脂分化的平衡遭到破壞導(dǎo)致的,，這些材料也將可以用于闡釋這種疾病的致病機制。(生物谷：towersimper編譯)

doi:10.1016/j.biomaterials.2011.11.061
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The balance of osteogenic and adipogenic differentiation in human mesenchymal stem cells by matrices that mimic stepwise tissue development

Takashi Hoshiba, Naoki Kawazoe, Guoping Chen

The disruption of balance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) leads to the disorders such as osteoporosis. Controlling the balance of these processes during MSC differentiation is important to maintain bone homeostasis. The extracellular microenvironment, especially the extracellular matrix (ECM), plays an important role in regulating MSC differentiation. Here, we investigated the role of ECM in controlling the balance between osteogenesis and adipogenesis of MSCs with matrices that mimic the stepwise tissue development of ECM during osteogenesis and adipogenesis. The osteogenesis of MSCs was enhanced by matrices with upregulated RUNX2 expression and suppressed PPARG expression, which mimic the attributes of the ECM during the early stages of osteogenesis. MSC adipogenesis was enhanced by matrices with suppressed expression of RUNX2, MSX2, and TAZ, which mimics the characteristics of ECM during the early stages of adipogenesis. These results showed that ECM may regulate the expression of various transcription factors to control the balance of osteogenesis and adipogenesis of MSCs. Tissue- and stage-specific ECM are required to control differentiation of MSCs into a specific cell types.