Embryonic Stem Cell Lines Accumulate Cancer-Causing Mutations

Embryonic stem cells have an incredible ability to grow in culture. Their ability to fill a culture dish in a short period of time makes them attractive candidates for regenerative medicine. However, embryonic stem cells bring a caveat to the table as well. They can sometimes form tumors. Many times these tumors are not aggressive, but sometimes they are. If embryonic stem cells are differentiated into tissues, their ability to grow and form tumors decreases, but does not completely disappear. There are plenty of cases where cells made from embryonic stem cells do not produce tumors when transplanted into animal hosts, but there are also several cases where even cells differentiated from embryonic stem cells can produce tumors.

Because scientists want to grow embryonic stem cell lines in the laboratory, they will grow them in cultures for long periods of time. However, growing human embryonic stem cells for long periods of time can cause the cell line to show chromosomal instability while being cultured continuously (Hanson C, Caisander G. Human embryonic stem cells and chromosome stability. APMIS. 2005 Nov-Dec; 113 (11-12): 751-5). Long-term growth of human embryonic stem (hES) cells in the laboratory can cause them to gain or lose large sections of chromosomes. According to several reports in Nature Biotechnology, this instability can lessen the reproducibility and reliability of experimental results, and can raise the specter of cancer, which can hinder the clinical application of embryonic stem cells.

Anselme Perrier and his colleagues of The Institute for Stem Cell Therapy in Evry, France discovered that long-term culture of five hES cell lines resulted in a the amplification of a portion of a the 20th chromosome called 20q.11.21 locus in four cases of the five cases (Nature Biotechnology 26, 1364 – 1366, 2008). This portion of the human genome contains 23 genes, many of which have roles in proliferation and cell survival.  Therefore, this amplification may give cells a selective advantage and therefore become more prevalent over time.

In a complementary study, Dr Claudia Spits of Vrije Universiteit Brussel in Belgium examined 17 different hES cell lines with her colleagues and showed the same amplification in five cases (Nature Biotechnology 26, 1361 – 1363, 2008).  A part of chromosome 18 was amplified in three cell lines and had several trisomies (three copies of a chromosome) and monosomies (one copy of a chromosome) as well.  The deletion of part of chromosome 18 led to rapid increase of cell growth, indicating that there may be a tumour suppressor in that area. “It’s still an early stage” says Spits, who intends to look further at chromosome 18. “The potentially oncogenic genes that lie in areas that are amplified or duplicated are not well characterized yet, but they have been found in a number of cancers.”

What are we to make of this?  Simply put, if embryonic stem cells are going to be used in a clinical setting, then they should be made and used within a short period of time.  Culturing them for long periods of time should be avoided, since this selects for cells that grow uncontrollably.  This might not be practical, but I think that there is enough evidence to suggest that making lines and culturing them for long periods should be taboo for clinically used lines.