制造逐阶段组织发育模拟基质材料,它们模拟间充质干细胞成骨分化和成脂分化期间的胞外基质。
日本国立材料科学研究所国际材料纳米建筑学研究中心组织再生材料部门成功地开发一种能够控制干细胞分化以便应用于再生医学的基质材料。2011年12月15日,这些研究结果在线发表《生物材料》(Biomaterials)期刊上。
要使得再生医学成为现实,人们必须能够诱导干细胞分化为特定细胞类型以便重建所需要的组织或器官来治疗疾病或缺陷。控制干细胞分化的技术是这一过程最为关键的方面。如今,人们正在关注胞外基质(extracellular matrix)——它在体内包围干细胞---在影响干细胞分化中的作用。然而,因为包围分化细胞(differentiating cell)的胞外基质是非常复杂的,而且根据分化的阶段它还会发生结构重塑,所以要模仿这种在不同阶段结构发生变化的基质制造出胞外基质材料一直是非常困难的。
在这篇研究中,研究小组成功地制造出两种类型的基质材料,它们都能模仿干细胞分化期间发生动态变化的胞外基质。它们是“逐阶段骨生成模仿基质(stepwise osteogenesis-mimicking matrix)”和“逐阶段脂肪生成模仿基质(stepwise adipogenesis-mimicking matrix)”,它们分别模仿间充质干细胞分化为成骨细胞(osteoblast)和脂肪细胞时的胞外基质。
使用这两种“逐阶段组织发育模仿基质(stepwise tissue development-mimicking matrix)”,研究人员成功地控制间充质干细胞的成骨分化和成脂分化。这些结果表明胞外基质在控制间充质干细胞的成骨发生和成脂发生平衡中发挥着重要的作用。
在未来,研究人员期待这种逐阶段组织发育模仿基质在阐释胞外基质在用于再生医学的诱导性多功能细胞、胚胎干细胞和其他干细胞分化时所发挥功能的研究中也起着一种关键性作用。基于骨质疏松症可能是成骨分化和成脂分化的平衡遭到破坏导致的,这些材料也将可以用于阐释这种疾病的致病机制。(生物谷:towersimper编译)
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.