A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic β Cells from Human Embryonic Stem Cells

Mirza Muhammad Fahd Qadir, Silvia Álvarez-Cubela, Kinsley Belle, Tamar Sapir, Fanuel Messaggio, Kevin B. Johnson, Oliver Umland, Darrell Hardin, Dagmar Klein, Ingrid Pérez-Álvarez, Fatima Sadiq, Oscar Alcázar, Luca A. Inverardi, Camillo Ricordi, Peter Buchwald, Christopher A. Fraker, Ricardo L. Pastori, Juan Domínguez-Bendala

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The transplantation of human embryonic stem cell (hESC)-derived insulin-producing β cells for the treatment of diabetes is finally approaching the clinical stage. However, even with state-of-the-art differentiation protocols, a significant percentage of undefined non-endocrine cell types are still generated. Most importantly, there is the potential for carry-over of non-differentiated cell types that may produce teratomas. We sought to modify hESCs so that their differentiated progeny could be selectively devoid of tumorigenic cells and enriched for cells of the desired phenotype (in this case, β cells). Here we report the generation of a modified hESC line harboring two suicide gene cassettes, whose expression results in cell death in the presence of specific pro-drugs. We show the efficacy of this system at enriching for β cells and eliminating tumorigenic ones both in vitro and in vivo. Our approach is innovative inasmuch as it allows for the preservation of the desired cells while eliminating those with the potential to develop teratomas. In this article, Domínguez-Bendala and colleagues present a strategy to modify pluripotent stem cells to allow for the selective destruction of tumorigenic escapees and/or fully developed teratomas, as well as for the specific selection of differentiated insulin-producing β-like cells. Cells engineered in this manner feature a double fail-safe mechanism designed to minimize the risks associated with their clinical transplantation.

Original languageEnglish (US)
Pages (from-to)611-623
Number of pages13
JournalStem Cell Reports
Issue number3
StatePublished - Mar 5 2019


  • beta cell differentiation
  • human embryonic stem cells
  • suicide genes
  • teratoma
  • transplantation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


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