A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers

Abstract 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...

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Autores principales:	Robert E. Rogers, Andrew Haskell, Berkley P. White, Sujata Dalal, Megan Lopez, Daniel Tahan, Simin Pan, Gagandeep Kaur, Hyemee Kim, Heather Barreda, Susan L. Woodard, Oscar R. Benavides, Jing Dai, Qingguo Zhao, Kristen C. Maitland, Arum Han, Zivko L. Nikolov, Fei Liu, Ryang Hwa Lee, Carl A. Gregory, Roland Kaunas
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	bioreactor immunomodulatory induced pluripotent stem cells mesenchymal stem cells Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/d7cc4d133b804c89858f1d897ac7c00b
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spelling	oai:doaj.org-article:d7cc4d133b804c89858f1d897ac7c00b2021-12-03T12:11:46ZA scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers2157-65802157-656410.1002/sctm.21-0151https://doaj.org/article/d7cc4d133b804c89858f1d897ac7c00b2021-12-01T00:00:00Zhttps://doi.org/10.1002/sctm.21-0151https://doaj.org/toc/2157-6564https://doaj.org/toc/2157-6580Abstract 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.Robert E. RogersAndrew HaskellBerkley P. WhiteSujata DalalMegan LopezDaniel TahanSimin PanGagandeep KaurHyemee KimHeather BarredaSusan L. WoodardOscar R. BenavidesJing DaiQingguo ZhaoKristen C. MaitlandArum HanZivko L. NikolovFei LiuRyang Hwa LeeCarl A. GregoryRoland KaunasWileyarticlebioreactorimmunomodulatoryinduced pluripotent stem cellsmesenchymal stem cellsMedicine (General)R5-920CytologyQH573-671ENStem Cells Translational Medicine, Vol 10, Iss 12, Pp 1650-1665 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bioreactor immunomodulatory induced pluripotent stem cells mesenchymal stem cells Medicine (General) R5-920 Cytology QH573-671
spellingShingle	bioreactor immunomodulatory induced pluripotent stem cells mesenchymal stem cells Medicine (General) R5-920 Cytology QH573-671 Robert E. Rogers Andrew Haskell Berkley P. White Sujata Dalal Megan Lopez Daniel Tahan Simin Pan Gagandeep Kaur Hyemee Kim Heather Barreda Susan L. Woodard Oscar R. Benavides Jing Dai Qingguo Zhao Kristen C. Maitland Arum Han Zivko L. Nikolov Fei Liu Ryang Hwa Lee Carl A. Gregory Roland Kaunas A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
description	Abstract 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.
format	article
author	Robert E. Rogers Andrew Haskell Berkley P. White Sujata Dalal Megan Lopez Daniel Tahan Simin Pan Gagandeep Kaur Hyemee Kim Heather Barreda Susan L. Woodard Oscar R. Benavides Jing Dai Qingguo Zhao Kristen C. Maitland Arum Han Zivko L. Nikolov Fei Liu Ryang Hwa Lee Carl A. Gregory Roland Kaunas
author_facet	Robert E. Rogers Andrew Haskell Berkley P. White Sujata Dalal Megan Lopez Daniel Tahan Simin Pan Gagandeep Kaur Hyemee Kim Heather Barreda Susan L. Woodard Oscar R. Benavides Jing Dai Qingguo Zhao Kristen C. Maitland Arum Han Zivko L. Nikolov Fei Liu Ryang Hwa Lee Carl A. Gregory Roland Kaunas
author_sort	Robert E. Rogers
title	A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
title_short	A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
title_full	A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
title_fullStr	A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
title_full_unstemmed	A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
title_sort	scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/d7cc4d133b804c89858f1d897ac7c00b
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A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers

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