, Volume 2, Issue 4, pp 266–276 | Cite as

Microwell Regulation of Pluripotent Stem Cell Self-Renewal and Differentiation

  • Cheston Hsiao
  • Sean P. PalecekEmail author


The fates of pluripotent stem cells (PSCs), including survival, self-renewal, and differentiation, are regulated by chemical and mechanical cues presented in the three-dimensional (3D) microenvironment. Most PSC studies have been performed on 2D substrates. However, 3D culture systems have demonstrated the importance of intercellular interactions in regulating PSC self-renewal and differentiation. Microwell culture systems have been developed to generate homogenous PSC colonies of defined sizes and shapes and to study how colony morphology affects cell fate. Using microwells, researchers have demonstrated that PSCs remain in a self-renewing undifferentiated state as a result of autocrine and paracrine signaling. Other studies have shown that microwell regulation of embryoid body size affects lineage commitment during differentiation via cell–cell contact and expression of soluble signals. In this review, we discuss recent advances in the design and utilization of 3D microwell platforms for studying intercellular regulation of PSC cell fate decisions and the underlying molecular mechanisms.


Microwells Pluripotent stem cells 3D microenvironment Cell fate 



This work was supported by NIH grant R01 EB007534 and NSF grant EFRI 0735903. We thank Samira Azarin for assistance in figure preparation.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Chemical and Biological EngineeringUniversity of Wisconsin–MadisonMadisonUSA

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