Impact of co-culture on pancreatic differentiation of embryonic stem cells

Ipsita Banerjee, Nripen Sharma, Martin Yarmush

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Promise of cellular therapy for type 1 diabetes has inspired the search for transplantable cell sources, and embryonic stem cells (ESCs) have emerged as strong candidates. We have developed a directed differentiation protocol to obtain insulin-producing cells from ESCs. The ESCs are first induced towards a homogeneous monolayer of definitive endoderm-like cells by co-culture with primary hepatocytes. Pancreatic commitment is induced by plating the ESC-derived endoderms on Matrigel, along with Sonic hedgehog inhibition and retinoid induction. More than 70% of differentiated cells positively upregulated Pdx-1, along with pro-endocrine transcription factors Ngn3, β2/neroD1, Nkx2.2 and Nkx6.1. Final maturation to islet-specific cells is achieved by co-culturing the ESC-derived pancreatic endocrine cells with endothelial cells, which resulted in Insulin 1 upregulation in 60% of the cell population, along with high levels of IAPP and Glut2. The differentiated cell population also secreted high levels of insulin. Our findings illustrate the significant effect of co-culture in different stages of differentiation and maturation of ESCs in vitro. Such a high yield of pancreatic islet cells has not yet been reported. Our findings establish a robust protocol for islet differentiation.

Original languageEnglish (US)
Pages (from-to)313-323
Number of pages11
JournalJournal of Tissue Engineering and Regenerative Medicine
Issue number4
StatePublished - Apr 2011

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering


  • Co-culture
  • Diabetes
  • Differentiation
  • Embryonic stem cell
  • Endothelial cell
  • Pancreatic islet


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