Bioinspired materials for controlling stem cell fate.

Bioinspired materials for controlling stem cell fate.
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DOI:
10.1021/ar900226q
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发表时间:
2010-03-16
影响因子:
18.3
通讯作者:
Peppas, Nicholas A.
Peppas, Nicholas A.
中科院分区:
化学1区
文献类型:
--
作者:
Fisher, Omar Z.;Khademhosseini, Ali;Langer, Robert;Peppas, Nicholas A.

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虽然研究人员目前模仿天然干细胞微环境的能力有限,但最近在干细胞生物学和生物材料科学的界面上的工作表明,用人工微环境控制干细胞行为是相当先进的。胚胎干细胞和成体干细胞是组织再生、基于细胞的治疗和用于药物筛选的皿中疾病模型的潜在有用平台。该领域的主要挑战是可靠地控制干细胞在体外的行为。常见的生物控制方案往往忽略材料科学家和工程师通常操纵的物理化学参数,如基材形貌和机械及流变性能。然而,通过适当关注这些参数,研究人员设计了新的合成微环境,以相当不自然的方式控制干细胞的行为。在本报告中,我们回顾了旨在克服自然生态位限制而不是模仿它们的合成微环境。仿生干细胞控制策略通常受限于对驱动干细胞从早期胚胎发育到成年晚期行为的复杂信号通路的不完全理解。干细胞的细胞外环境呈现出一种混杂的竞争性生物信号,使细胞处于不稳定的平衡状态。使用合成聚合物,研究人员设计了合成微环境,其中包含一系列整齐的细胞信号,包括特异性和非特异性,这些信号是由生物学激发的,而不是模仿生物学。这些已被证明是有用的,在维持细胞的潜能,研究不对称细胞分裂,并控制cellulardifferentiation.We讨论最近的研究,突出了重要的生物材料的性能控制干细胞的行为,以及先进的工艺选择这些材料,如组合和高通量筛选。这项工作的大部分都利用了微米和纳米级的制造工具来控制材料的性能,并在二维和三维空间中产生多样性。由于其易于合成且与生物软物质相似,水凝胶已成为生成3D微环境的首选生物材料。在合成生物学的框架内介绍这些努力时,我们预计未来的研究人员可能会利用合成聚合物来创造以临床相关方式控制干细胞行为的微环境。
Although researchers currently have limited ability to mimic the natural stem cell microenvironment, recent work at the interface of stem biology and biomaterials science has demonstrated that control over stem cell behavior with artificial microenvironments is quite advanced. Embryonic and adult stem cells are potentially useful platforms for tissue regeneration, cell-based therapeutics, and disease-in-a-dish models for drug screening. The major challenge in this field is to reliably control stem cell behavior outside the body. Common biological control schemes often ignore physicochemical parameters that materials scientists and engineers commonly manipulate, such as substrate topography and mechanical and rheological properties. However, with appropriate attention to these parameters, researchers have designed novel synthetic microenvironments to control stem cell behavior in rather unnatural ways.In this Account, we review synthetic microenvironments that aim to overcome the limitations of natural niches rather than to mimic them. A biomimetic stem cell control strategy is often limited by an incomplete understanding of the complex signaling pathways that drive stem cell behavior from early embryogenesis to late adulthood. The stem cell extracellular environment presents a miscellany of competing biological signals that keep the cell in a state of unstable equilibrium. Using synthetic polymers, researchers have designed synthetic microenvironments with an uncluttered array of cell signals, both specific and nonspecific, that are motivated by rather than modeled after biology. These have proven useful in maintaining cell potency, studying asymmetric cell division, and controlling cellular differentiation.We discuss recent research that highlights important biomaterials properties for controlling stem cell behavior, as well as advanced processes for selecting those materials, such as combinatorial and high-throughput screening. Much of this work has utilized micro- and nanoscale fabrication tools for controlling material properties and generating diversity in both two and three dimensions. Because of their ease of synthesis and similarity to biological soft matter, hydrogels have become a biomaterial of choice for generating 3D microenvironments. In presenting these efforts within the framework of synthetic biology, we anticipate that future researchers may exploit synthetic polymers to create microenvironments that control stem cell behavior in clinically relevant ways.
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