Health,Stem Cells, and Technology

Sunday, December 4, 2011

Genetic And Epigenetic Stability of Stem Cells

While it is reassuring that 75% of the stem cell lines studied remained normal after prolonged growth in the laboratory, detecting and eliminating abnormal cells is an absolute prerequisite for clinical use of stem cell products.

The aforementioned is the take home message from scientists at the University of Melbourne, University of NSW and CSIRO who contributed to this study that examined how the genome of 138 stem cell lines of diverse ethnic backgrounds changed when the cells were grown in the laboratory.

An international study, published this week in the journal Nature Biotechnology, reveals more about human pluripotent stem cells and their genetic stability and has important implications for the development of therapies using these cells.

Single-nucleotide polymorphism (SNP) analysis revealed that the cultures included representatives of most major ethnic groups. Most lines remained karyotypically (chromosome image analysis) normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.

Dr. Martin Pera, Ph.D., Professor and Chair of Stem Cell Science at the University of Melbourne and Program Leader of Stem Cells Australia, led the collaborative study from the International Stem Cell Initiative that was the largest survey of its kind on the genetic and epigenetic stability of human embryonic stem cell and induced pluripotent stem cells.