Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation
Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation
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DOI：
10.1002/jbm.a.32710
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发表时间：
2010-08-01
影响因子：
4.9
通讯作者：
McDevitt, Todd C.
中科院分区：
文献类型：
--
作者：
Carpenedo, Richard L.;Seaman, Scott A.;McDevitt, Todd C.
多能胚胎干细胞 (ESC) 在体外通过称为胚状体 (EB) 的多细胞球体进行分化，通常用于模拟早期哺乳动物发育的各个方面，并启动再生医学技术的细胞分化。然而，EB 的三维性质对 ESC 定向分化提出了独特的挑战，包括能够指定细胞命运的形态发生分子有限扩散到 EB 中。 EB 中掺入的可降解聚合物微球可以以时空控制的方式向 ESC 提供形态发生分子，从而更有效地指导分化。在这项研究中，评估了微球尺寸对 EB 掺入和 ESC 分化（响应微球介导的形态发生素递送）的影响。制备平均直径为 1、3 或 11 μm 的 PLGA 微球，并在 EB 形成过程中与 ESC 混合。较小的微球比较大的微球更有效地融入整个 EB，并且无论大小如何，都能保留至少 10 天的分化。从掺入的微球中释放的视黄酸以尺寸依赖性方式诱导 EB 空化，较小的微球比较大的颗粒触发加速且更完全的空化。这些结果表明，对干细胞环境中微球递送载体的尺寸进行改造可用于调节分化过程。 (C) 2010 Wiley periodicals, Inc. J Biomed Mater Res 94A: 466-475, 2010
Differentiation of pluripotent embryonic stem cells (ESCs) in vitro via multicellular spheroids called embryoid bodies (EBs) is commonly performed to model aspects of early mammalian development and initiate differentiation of cells for regenerative medicine technologies. However, the three-dimensional nature of EBs poses unique challenges for directed ESC differentiation, including limited diffusion into EBs of morphogenic molecules capable of specifying cell fate. Degradable polymer microspheres incorporated within EBs can present morphogenic molecules to ESCs in a spatiotemporally controlled manner to more efficiently direct differentiation. In this study, the effect of microsphere size on incorporation into EBs and ESC differentiation in response to microsphere-mediated morphogen delivery were assessed. PLGA microspheres with mean diameters of 1, 3, or 11 mu m were fabricated and mixed with ESCs during EB formation. Smaller microspheres were incorporated more efficiently throughout EBs than larger microspheres, and regardless of size, retained for at least 10 days of differentiation. Retinoic acid release from incorporated microspheres induced EB cavitation in a size-dependent manner, with smaller microspheres triggering accelerated and more complete cavitation than larger particles. These results demonstrate that engineering the size of microsphere delivery vehicles incorporated within stem cell environments can be used to modulate the course of differentiation. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res 94A: 466-475, 2010