It has been widely reported that human pluripotent stem cells (hPSCs) can become karyotypically unstable during their prolonged culture in vitro (1-4). These cytogenetic changes bear stark similarities to those found in many human cancers raising safety concerns for their potential use in regenerative medicine. Although the mechanisms behind these changes are still to be elucidated, they have been shown to provide variant cells with a selective advantage and rapidly out-compete normal cells in culture.

Characteristics of karyotypically abnormal hPSCs include resistance to apoptosis, altered differentiation patterns and persistent stem cells populations in teratomas. As the first clinical trials using hPSC-derived cells are underway, it is imperative that we understand the implications of these changes and how to detect and minimize their occurrence in hPSC cultures.

“Safety of hPSC-derived cellular products is the first and foremost requirement for fulfillment of hPSC clinical potential,” says Dr. Ivana Barbaric, Lecturer and Principal Investigator at the Centre for Stem Cell Biology, the University of Sheffield. “Genome stability of hPSCs is of particular concern given the association of genetic changes and malignant phenotype in cancerous cells. In addition to mutational rates, the selection pressures that cells experience during the single-cell passaging may play a role in the appearance of genetically variant cells in cultures.” [Read more…]