Microcarriers are synthetic particles used in bioreactor‐based cell manufacturing of anchorage‐dependent cells to promote proliferation at efficient physical volumes, mainly by increasing the surface area‐to‐volume ratio. Mesenchymal stromal cells (MSCs) are adherent cells that are used for numerous clinical trials of autologous and allogeneic cell therapy, thus requiring avenues for large‐scale cell production at efficiently low volumes and cost. Here, a dissolvable gelatin‐based microcarrier is developed for MSC expansion. This novel microcarrier shows comparable cell attachment efficiency and proliferation rate when compared to several commercial microcarriers, but with higher harvesting yield due to the direct dissolution of microcarrier particles and thus reduced cell loss at the cell harvesting step. Furthermore, gene expression and in vitro differentiation suggest that MSCs cultured on gelatin microcarriers maintain trilineage differentiation with similar adipogenic differentiation efficiency and higher chondrogenic and osteogenic differentiation efficiency when compared to MSCs cultured on 2D planar polystyrene tissue culture flask; on the contrary, MSCs cultured on conventional microcarriers appear to be bipotent along osteochondral lineages whereby adipogenic differentiation potential is impeded. These results suggest that these gelatin microcarriers are suitable for MSC culture and expansion, and can also potentially be extended for other types of anchorage‐dependent cells.

中文翻译：

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可溶的基于明胶的微载体，通过微流控微滴产生，用于间充质基质细胞的扩增和培养

微载体是合成颗粒，用于锚固依赖性细胞的生物反应器细胞制造中，主要通过增加表面积体积比来促进有效物理体积下的增殖。间充质基质细胞（MSC）是贴壁细胞，用于自体和异体细胞疗法的众多临床试验，因此需要以有效的小批量生产和低成本来大规模生产细胞的途径。在这里，开发了一种可溶解的基于明胶的微载体，用于MSC扩增。与几种市售微载体相比，这种新型微载体显示出可比的细胞附着效率和增殖速率，但由于微载体颗粒的直接溶解，因此收获率更高，从而减少了细胞收获步骤的细胞损失。此外，基因表达和体外分化表明，与在2D平面聚苯乙烯组织培养瓶上培养的MSC相比，在明胶微载体上培养的MSC保持三系分化，具有相似的成脂分化效率，以及更高的成软骨和成骨分化效率。相反，在常规微载体上培养的MSC沿骨软骨谱系似乎是双能的，从而阻碍了成脂分化潜能。这些结果表明，这些明胶微载体适用于MSC的培养和扩增，还可能扩展至其他类型的锚定依赖性细胞。