A team of researchers at the Harvard Stem Cell Institute, working in collaboration with investigators at the Broad Institute of MIT and Harvard, has identified the gene mutation that leads to uncontrolled cell division and tumor formation in some stem cell lines. The Harvard scientists say the findings suggest the need to screen lab-grown stem cells for such mutations.
Cancer Risk with Stem Cell Therapy
The research indicates that indiscriminate use of stem cell therapies could lead to an elevated risk of cancer in patients receiving stem cell transplants. The team identified acquired mutations in p53, a gene that is responsible for controlling cell growth and suppressing tumor formation. The findings were published in the journal Nature.
Harvard Scientists Say Lab-Grown Stem Cells Must Be Screened
Lab-grown stem cells can acquire mutations just like stem cells in the body. The team discovered one such precancerous mutation which increases an individual’s risk of blood cancer by 12-fold. Stem cells with this type of mutation can quickly outnumber other cells and take over the tissue. This type of clonal selection is observed in the body during tumor formation and is also routinely noted in laboratory cultures.
The findings should not discourage the study of novel experimental therapies, say the scientists. However, there is a need to proceed with caution, explains Kevin Eggan, Director of Stem Cell Biology at the Stanley Center for Psychiatric Research. Fortunately, current gene sequencing technology allows these checks to be performed in a sensitive, precise, and inexpensive manner.
Experiments in Stem Cell Mutations
The researchers genetically analyzed 140 lines of stem cells and were surprised to find that approximately 5 percent of them had an acquired mutation of p53, a tumor-suppressing gene which has been nicknamed a guardian of the genome because of its protective effect. People with a mutation of p53 suffer from Li-Fraumeni syndrome, a rare disorder associated with a nearly 100 percent chance of developing cancers in various tissues of the body. Interestingly, even a single mutation in p53 can compromise the function of the protein it produces. This type of dominant negative mutation is a common cause of human cancers.
The key finding of the study was that a single p53 mutant cell could multiply and quickly overpower a culture of 1 million healthy stem cells. This reiterates the need to screen stem cells before they are transplanted into patients. Gene-sequencing tests are relatively inexpensive and allow scientists to remove mutated cells from cell cultures before they are transplanted. This ensures that cells derived from induced pluripotent stem cells are free of dangerous cancer-causing mutations.