Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules.
Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules.
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DOI：
10.1159/000514580
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Dumbleton J;Shamul JG;Jiang B;Agarwal P;Huang H;Jia X;He X
胚胎干细胞（ESC）的定向神经分化已被广泛研究，以改善神经退行性疾病的治疗。这可以通过基质细胞衍生的诱导活性（SDIA），通过在饲养基质细胞层上直接培养ESC来完成。然而，干细胞在分化过程中通常与饲养细胞混合，使得难以获得纯的分化细胞群以供进一步使用。为了解决这个问题，这里使用非平面微流体装置将鼠ESC（mESC）封装在具有不同尺寸的藻酸盐水凝胶壳的微胶囊的3D液体核心中，用于通过SDIA进行早期神经分化，通过在PA 6细胞的饲养层上培养载有mESC的微胶囊。此外，通过氧化或RGD肽缀合来修饰微胶囊的藻酸盐水凝胶壳，以检查对包封的mESC聚集体的神经分化的机械和化学作用。巢蛋白在包封在小（~300 μm）微胶囊中的聚集体中观察到较高的表达，并在PA 6细胞饲养层上培养。此外，用RGD修饰藻酸盐有利于微胶囊内的早期神经突延伸。这项研究表明，RGD肽的存在，PA 6细胞的SDIA效应，以及培养基中白血病抑制因子（LIF）的缺乏，可以导致mESC在小微胶囊的3D微环境中具有广泛的神经突的早期分化。这是第一项研究，以探讨细胞粘附和降解的封装材料的定向神经分化的mESCs的影响。简单的修改（即，用于改善mESC的早期神经分化的小型化3D环境的氧化和RGD掺入）可能潜在地增强mESC进一步下游分化为更特化的神经元以用于治疗用途和药物筛选。
Directed neural differentiation of embryonic stem cells (ESCs) has been studied extensively to improve the treatment of neurodegenerative disorders. This can be done through stromal-cell derived inducing activity (SDIA), by culturing ESCs directly on top of a layer of feeder stromal cells. However, the stem cells usually become mixed with the feeder cells during the differentiation process, making it difficult to obtain a pure population of the differentiated cells for further use. To address this issue, a non-planar microfluidic device is used here to encapsulate murine ESCs (mESCs) in the 3D liquid core of microcapsules with an alginate hydrogel shell of different sizes for early neural differentiation through SDIA, by culturing mESC-laden microcapsules over a feeder layer of PA6 cells. Furthermore, the alginate hydrogel shell of the microcapsules is modified via oxidation or RGD peptide conjugation to examine the mechanical and chemical effects on neural differentiation of the encapsulated mESC aggregates. A higher expression of Nestin is observed in the aggregates encapsulated in small (~300 μm) microcapsules and cultured over the PA6 cell feeder layer. Furthermore, the modification of the alginate with RGD facilitates early neurite extension within the microcapsules. This study demonstrates that the presence of the RGD peptide, the SDIA effect of the PA6 cells, and the absence of leukemia inhibition factor (LIF) from the medium can lead to the early differentiation of mESCs with extensive neurites within the 3D microenvironment of the small microcapsules. This is the first study to investigate the effects of cell adhesion and degradation of the encapsulation materials for directed neural differentiation of mESCs. The simple modifications (i.e., oxidation and RGD incorporation) of the miniaturized 3D environment for improved early neural differentiation of mESCs may potentially enhance further downstream differentiation of the mESCs into more specialized neurons for therapeutic use and drug screening.
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影响因子：
6.1
作者：
Park, Jaesung;Cho, Cheul H.;Yarmush, Martin L.
通讯作者：
Yarmush, Martin L.
影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
早期胚胎发育的生物启动复杂性以及组织工程和再生医学的生物启发的复杂性。
影响因子：
5.8
作者：
He X
通讯作者：
He X
DOI：
10.1111/febs.14607
发表时间：
2018-10
期刊：
The FEBS journal
影响因子：
--
作者：
Surmeier DJ
通讯作者：
Surmeier DJ
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ