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

Sci Rep. 2021 Mar 30;11(1):7177. doi: 10.1038/s41598-021-85786-2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors
  • Capsules / chemistry
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Line
  • Cell Survival
  • Cell Transplantation / methods
  • Diabetes Mellitus / therapy
  • End Stage Liver Disease / therapy
  • Humans
  • Hydrogels / chemistry
  • Insulin-Secreting Cells / physiology
  • Microfluidic Analytical Techniques / instrumentation
  • Pluripotent Stem Cells / physiology*
  • Pluripotent Stem Cells / transplantation
  • Polyethylene Glycols / chemistry
  • Spheroids, Cellular / physiology*

Substances

  • Capsules
  • Hydrogels
  • Polyethylene Glycols