Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.
Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.
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DOI：
10.1002/adhm.202201138
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发表时间：
2022-12
影响因子：
10
通讯作者：
Skylar-Scott, Mark A. A.
中科院分区：
文献类型：
--
作者：
Ho, Debbie L. L.;Lee, Stacey;Du, Jianyi;Weiss, Jonathan D. D.;Tam, Tony;Sinha, Soham;Klinger, Danielle;Devine, Sean;Hamfeldt, Art;Leng, Hope T. T.;Herrmann, Jessica E. E.;He, Mengdi;Fradkin, Lee G. G.;Tan, Tze Kai;Standish, David;Tomasello, Peter;Traul, Donald;Dianat, Noushin;Ladi, Rukmini;Vicard, Quentin;Katikireddy, Kishore;Skylar-Scott, Mark A. A.
将数十亿个细胞的可持续文化和全细胞生物互联的生物印刷提供了一种器官范围的组织工程，这是由于成本，空间和处理的限制，因此可以固定地延伸。 Ology和在两个不同的细胞系中，在三个序列上保持多元标记的表达可以是Subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture‐to‐3D bioprinting pipeline that enables a sustainable十亿个细胞尺度器官工程的方法。
实践制造的无需细胞固体器官的艺术需要在这里产生数十亿个干细胞，以期在自动化生物反应器系统中提出了多达40亿人类诱导的人类诱导的多能干细胞。
Combining the sustainable culture of billions of human cells and the bioprinting of wholly cellular bioinks offers a pathway toward organ‐scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, the suspension culture of human induced pluripotent stem cell‐derived aggregates (hAs) is optimized using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, it is demonstrated that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. This 4‐day culture results in a 16.6‐ to 20.4‐fold expansion of cells, generating approximately 4 billion cells per vessel, while maintaining >94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture‐to‐3D bioprinting pipeline that enables a sustainable approach to billion cell‐scale organ engineering. Practicing the art of manufacturing densely cellular solid organs on demand will require the production of billions of stem cells. Here, an optimized pipeline is presented for growing up to 4 billion human induced pluripotent stem cells in automated bioreactor systems. These stem cell aggregates are compacted into viscoelastic and wholly cellular bioinks and are subsequently bioprinted and differentiated.
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影响因子：
5.2
作者：
Dekel-Naftali, Michal;Aviram-Goldring, Ayala;Rienstein, Shlomit
通讯作者：
Rienstein, Shlomit
影响因子：
9
作者：
Goulart, Ernesto;de Caires-Junior, Luiz Carlos;Zatz, Mayana
通讯作者：
Zatz, Mayana
DOI：
10.1126/science.aav9750
发表时间：
2019-05-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Grigoryan B;Paulsen SJ;Corbett DC;Sazer DW;Fortin CL;Zaita AJ;Greenfield PT;Calafat NJ;Gounley JP;Ta AH;Johansson F;Randles A;Rosenkrantz JE;Louis-Rosenberg JD;Galie PA;Stevens KR;Miller JS
通讯作者：
Miller JS
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP
影响因子：
6
作者：
Cooke ME;Rosenzweig DH
通讯作者：
Rosenzweig DH