Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor

Pouria Fattahi; Ali Rahimian; Michael Q. Slama; Kihak Gwon; Alan M. Gonzalez-Suarez; Jadon Wolf; Harihara Baskaran; Caden D. Duffy; Gulnaz Stybayeva; Quinn P. Peterson; Alexander Revzin

doi:10.1038/s41598-021-85786-2

Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor

Pouria Fattahi
, Ali Rahimian
, Michael Q. Slama
, Kihak Gwon
, Alan M. Gonzalez-Suarez
, Jadon Wolf
, Harihara Baskaran
, Caden D. Duffy
, Gulnaz Stybayeva
, Quinn P. Peterson
, Alexander Revzin

Department of Biofibers and Biomaterials Science

Mayo Clinic College of Medicine and Science
Case Western Reserve University

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

Cellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.

Original language	English
Article number	7177
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-85786-2
State	Published - Dec 2021

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Fattahi, P., Rahimian, A., Slama, M. Q., Gwon, K., Gonzalez-Suarez, A. M., Wolf, J., Baskaran, H., Duffy, C. D., Stybayeva, G., Peterson, Q. P., & Revzin, A. (2021). Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor. Scientific Reports, 11(1), Article 7177. https://doi.org/10.1038/s41598-021-85786-2

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title = "Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor",

abstract = "Cellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.",

author = "Pouria Fattahi and Ali Rahimian and Slama, \{Michael Q.\} and Kihak Gwon and Gonzalez-Suarez, \{Alan M.\} and Jadon Wolf and Harihara Baskaran and Duffy, \{Caden D.\} and Gulnaz Stybayeva and Peterson, \{Quinn P.\} and Alexander Revzin",

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Fattahi, P, Rahimian, A, Slama, MQ, Gwon, K, Gonzalez-Suarez, AM, Wolf, J, Baskaran, H, Duffy, CD, Stybayeva, G, Peterson, QP & Revzin, A 2021, 'Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor', Scientific Reports, vol. 11, no. 1, 7177. https://doi.org/10.1038/s41598-021-85786-2

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T1 - Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor

AU - Fattahi, Pouria

AU - Rahimian, Ali

AU - Slama, Michael Q.

AU - Gwon, Kihak

AU - Gonzalez-Suarez, Alan M.

AU - Wolf, Jadon

AU - Baskaran, Harihara

AU - Duffy, Caden D.

AU - Stybayeva, Gulnaz

AU - Peterson, Quinn P.

AU - Revzin, Alexander

PY - 2021/12

Y1 - 2021/12

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AB - Cellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.

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DO - 10.1038/s41598-021-85786-2

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SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

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ER -

Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor

Abstract

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