Incorporation of biomaterials in multicellular aggregates modulates pluripotent stem cell differentiation.
Incorporation of biomaterials in multicellular aggregates modulates pluripotent stem cell differentiation.
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DOI：
10.1016/j.biomaterials.2010.08.113
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发表时间：
2011-01
期刊：
影响因子：
14
通讯作者：
McDevitt, Todd C.
中科院分区：
文献类型：
--
作者：
Bratt-Leal, Andres M.;Carpenedo, Richard L.;Ungrin, Mark D.;Zandstra, Peter W.;McDevitt, Todd C.
生物材料越来越多地被用来设计细胞外干细胞微环境的生化和生物物理特性，以便定制生态位特征和指导细胞表型。到目前为止，干细胞与生物材料的相互作用主要是通过将干细胞引入人工环境中来进行的，例如在生物材料表面进行2D细胞培养，在水凝胶材料中包裹细胞悬浮液，或者在3D聚合物支架上种植细胞。在本研究中，从不同材料(如琼脂糖、PLGA和明胶)制备的微粒在分化前以剂量依赖的方式稳定地整合在多潜能干细胞(PSCs)聚集体中，作为一种直接在3D中检测干细胞-生物材料相互作用的手段。有趣的是，干细胞聚集体中物质的存在差异化地调节了几个分化标记物的基因和蛋白质表达模式，而不会对细胞活力产生不利影响。三维干细胞聚集体中的微粒掺入可以控制细胞外环境信号(即可溶性因子、细胞外基质和细胞间黏附分子)的空间呈现，作为指导干细胞分化的一种手段，用于组织工程和再生医学应用。此外，这些结果表明，干细胞聚集体中微粒的物理存在并不影响PSC的分化，但事实上，生物材料的选择可以影响干细胞采用特定分化细胞表型的倾向。
Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell-biomaterial interactions have largely been studied by introducing stem cells into artificial environments, such as 2D cell culture on biomaterial surfaces, encapsulation of cell suspensions within hydrogel materials, or cell seeding on 3D polymeric scaffolds. In this study, microparticles fabricated from different materials, such as agarose, PLGA and gelatin, were stably integrated, in a dose-dependent manner, within aggregates of pluripotent stem cells (PSCs) prior to differentiation as a means to directly examine stem cell-biomaterial interactions in 3D. Interestingly, the presence of the materials within the stem cell aggregates differentially modulated the gene and protein expression patterns of several differentiation markers without adversely affecting cell viability. Microparticle incorporation within 3D stem cell aggregates can control the spatial presentation of extracellular environmental cues (i.e. soluble factors, extracellular matrix and intercellular adhesion molecules) as a means to direct the differentiation of stem cells for tissue engineering and regenerative medicine applications. In addition, these results suggest that the physical presence of microparticles within stem cell aggregates does not compromise PSC differentiation, but in fact the choice of biomaterials can impact the propensity of stem cells to adopt particular differentiated cell phenotypes.
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影响因子：
14
作者：
Carpenedo, Richard L.;Bratt-Leal, Andrs M.;Marklein, Ross A.;Seaman, Scott A.;Bowen, Nathan J.;McDonald, John F.;McDevitt, Todd C.
通讯作者：
McDevitt, Todd C.
影响因子：
4.9
作者：
Carpenedo, Richard L.;Seaman, Scott A.;McDevitt, Todd C.
通讯作者：
McDevitt, Todd C.
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
DOI：
10.1073/pnas.1735463100
发表时间：
2003-10-28
影响因子：
11.1
作者：
Levenberg, S;Huang, NF;Langer, R
通讯作者：
Langer, R
影响因子：
14
作者：
Rahman, Nafees;Purpura, Kelly A.;Shoichet, Molly S.
通讯作者：
Shoichet, Molly S.