A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers,STEM CELLS Translational Medicine

当前位置： X-MOL 学术 › Stem Cells Transl. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-09-10 , DOI: 10.1002/sctm.21-0151
Robert E Rogers ₁ , Andrew Haskell ₁ , Berkley P White ₂ , Sujata Dalal ₁ , Megan Lopez ₁ , Daniel Tahan ₁ , Simin Pan ₁ , Gagandeep Kaur ₁ , Hyemee Kim ₁ , Heather Barreda ₁ , Susan L Woodard ₃ , Oscar R Benavides ₂ , Jing Dai ₄ , Qingguo Zhao ₁ , Kristen C Maitland ₂ , Arum Han _{2,

4} , Zivko L Nikolov _{3,

5} , Fei Liu ₁ , Ryang Hwa Lee ₁ , Carl A Gregory ₁ , Roland Kaunas ₂

Affiliation

Human mesenchymal stem cells (hMSCs) are effective in treating disorders resulting from an inflammatory or heightened immune response. The hMSCs derived from induced pluripotent stem cells (ihMSCs) share the characteristics of tissue derived hMSCs but lack challenges associated with limited tissue sources and donor variation. To meet the expected future demand for ihMSCs, there is a need to develop scalable methods for their production at clinical yields while retaining immunomodulatory efficacy. Herein, we describe a platform for the scalable expansion and rapid harvest of ihMSCs with robust immunomodulatory activity using degradable gelatin methacryloyl (GelMA) microcarriers. GelMA microcarriers were rapidly and reproducibly fabricated using a custom microfluidic step emulsification device at relatively low cost. Using vertical wheel bioreactors, 8.8 to 16.3-fold expansion of ihMSCs was achieved over 8 days. Complete recovery by 5-minute digestion of the microcarriers with standard cell dissociation reagents resulted in >95% viability. The ihMSCs matched or exceeded immunomodulatory potential in vitro when compared with ihMSCs expanded on monolayers. This is the first description of a robust, scalable, and cost-effective method for generation of immunomodulatory ihMSCs, representing a significant contribution to their translational potential.

中文翻译：

一种利用生物反应器和可降解微载体从诱导多能细胞中产生间充质干细胞的可扩展系统

人间充质干细胞 (hMSC) 可有效治疗由炎症或免疫反应增强引起的疾病。源自诱导多能干细胞 (ihMSCs) 的 hMSCs 具有组织衍生的 hMSCs 的特征，但缺乏与有限的组织来源和供体变异相关的挑战。为了满足对 ihMSC 的预期未来需求，需要开发可扩展的方法，以临床产量生产它们，同时保持免疫调节功效。在这里，我们描述了一个使用可降解明胶甲基丙烯酰 (GelMA) 微载体可扩展和快速收获具有强大免疫调节活性的 ihMSCs 的平台。GelMA 微载体使用定制的微流体步进乳化装置以相对较低的成本快速且可重复地制造。使用垂直轮式生物反应器，在 8 天内，ihMSC 扩增了 8.8 到 16.3 倍。通过用标准细胞解离试剂消化微载体 5 分钟完全恢复导致 > 95% 的活力。与在单层上扩增的 ihMSCs 相比，ihMSCs 在体外匹配或超过免疫调节潜力。这是对生成免疫调节 ihMSCs 的稳健、可扩展且具有成本效益的方法的首次描述，代表了对其转化潜力的重大贡献。

更新日期：2021-09-10

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11