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.”
Dr. Barbaric, together with Professor Peter Andrews, will be discussing the causes and consequences of genetic changes in hPSCs and approaches to minimize their occurrence in hPSC cultures at the live webinar featured in STEMCELL Technologies’ Pluripotent Learning Lounge.
Genetic Stability of Human Pluripotent Stem Cells
Prof. Peter Andrews and Dr. Ivana Barbaric
Europe: Wednesday, October 5th, 2016. 3pm BST, 4pm CEST
North America: Wednesday, October 5th, 2016. 7am PDT, 10am EDT
Registration is open at the Pluripotent Learning Lounge.
The Pluripotent Learning Lounge webinar series feature key figures in human pluripotent stem cell research. Recent webinar presenters include Prof. Janet Rossant of Hospital for Sick Children and Dr. Chad Cowan of Harvard University. Topics range from the generation of patient-specific hPSCs for disease modeling to lineage-specific differentiations, such as beta cells, hepatocytes and lung cells. Visit the lounge to watch more webinars, learn about the speakers, and read speaker interviews.
- Draper, JS et al. (2004) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechol 22(1): 53-4.
- International Stem Cell Initiative (2011) Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Technol 29(12): 1132-44.
- Barbaric, I et al. (2014) Time-lapse analysis of human embryonic stem cells reveals multiple bottlenecks restricting colony formation and their relief upon culture adaptation. Stem Cell Reports 3(1): 142-55.
- Garitaonandia, I et al. (2015) Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions. PLoS One 10(2): e0118307.