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微载体支持的搅拌悬浮生物反应器中巨核细胞的大规模生产。

Large-scale production of megakaryocytes in microcarrier-supported stirred suspension bioreactors.

机构信息

Institute for Transfusion Medicine, Hannover Medical School, Hannover, 30625, Germany.

REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, 30625, Germany.

出版信息

Sci Rep. 2018 Jul 5;8(1):10146. doi: 10.1038/s41598-018-28459-x.

DOI:10.1038/s41598-018-28459-x
PMID:29977045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6033877/
Abstract

Megakaryocytes (MKs) are the precursors of platelets (PLTs) and may be used for PLT production in vivo or in vitro, as well as a source for PLT-derived growth factors. Induced pluripotent stem cells represent an unlimited cell source for the in vitro production of MKs. This study aimed at developing an effective, xeno-free and scalable system to produce high numbers of MKs. In particular, microcarrier beads-assisted stirred bioreactors were evaluated as a means of improving MK yields. This method resulted in the production of 18.7 × 10 MKs per 50 ml medium. Laminin-coated microcarriers increased MK production per iPSC by up to 10-fold. MKs obtained in this system showed typical features of mature MKs and were able to produce PLTs in vitro and in vivo. To increase safety, MKs produced in the bioreactors were irradiated; a procedure that did not affect their capability to form proPLTs and PTLs after transfusion. In vitro generated MKs represent a promising alternative to donor PLTs and open the possibility for the development of innovative MK-based cell therapies.

摘要

巨核细胞（MKs）是血小板（PLTs）的前体细胞，可用于体内或体外的 PLT 生产，以及 PLT 衍生生长因子的来源。诱导多能干细胞代表了体外生产 MKs 的无限细胞来源。本研究旨在开发一种有效、无动物源且可扩展的系统，以生产大量的 MKs。特别是，微载体珠辅助搅拌式生物反应器被评估为提高 MK 产量的一种手段。这种方法可生产 18.7×10 的 MKs/50ml 培养基。层粘连蛋白包被的微载体使每个 iPSC 的 MK 产量增加了 10 倍。从该系统获得的 MKs 表现出成熟 MK 的典型特征，并且能够在体外和体内产生 PLTs。为了提高安全性，在生物反应器中生产的 MKs 进行了辐照；该过程不影响它们在输注后形成 proPLTs 和 PTLs 的能力。体外生成的 MKs 是供体 PLTs 的有前途的替代品，并为开发基于 MK 的创新细胞疗法开辟了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/e38a5ded7094/41598_2018_28459_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/9e7ba47c520f/41598_2018_28459_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/21122e5ff975/41598_2018_28459_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/2eb9f923a55b/41598_2018_28459_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/f2f23ce62611/41598_2018_28459_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/d477169baee4/41598_2018_28459_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/453603de3eb5/41598_2018_28459_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/e38a5ded7094/41598_2018_28459_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/9e7ba47c520f/41598_2018_28459_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/21122e5ff975/41598_2018_28459_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/2eb9f923a55b/41598_2018_28459_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/f2f23ce62611/41598_2018_28459_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/d477169baee4/41598_2018_28459_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/453603de3eb5/41598_2018_28459_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/6033877/e38a5ded7094/41598_2018_28459_Fig7_HTML.jpg

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