Author Interviews, FASEB, Genetic Research, Stanford / 26.01.2015
Lab Finds Way To Lengthen Short Telomeres
MedicalResearch.com Interview with:
Dr. John Ramunas PhD
Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California
Medical Research: What is the background for this study?
Dr. Ramunas: Telomeres comprise repetitive DNA sequences at the ends of chromosomes. Telomeres protect the ends of chromosomes, but become shorter with each cell division and due to oxidative damage. Critically short telomeres are implicated in diseases of aging and devastating genetic disorders of insufficient telomere maintenance .
Medical Research: What are the main findings?
Dr. Ramunas: Our main finding is that telomeres in human cells can be lengthened by a new method with therapeutic potential. We delivered modified mRNA encoding TERT, the protein component of telomerase, the enzyme that increases the length of telomeres by adding DNA repeats. The protein TERT is usually the rate limiting component of the enzyme. In this study, we used four groups of cells. The first group received modified mRNA encoding TERT, and the other three groups were controls that received either mRNA encoding an inactive form of TERT, the solution in which TERT is delivered, or no treatment. The telomeres of the first group (telomere extending treatment group) were extended rapidly over a period of a few days, whereas the telomeres of the three control groups were not extended. The first group was also able to undergo more cell divisions, whereas the controls were not. Importantly for the potential safety of our approach, the telomeres of the first group resumed shortening after they were extended. This is important because it shows that due to the short, transient treatment, the cells were not immortalized, ie. not tumorigenic. Further, all of the cell populations treated to date eventually stopped dividing, further indicating that they were not immortalized. We have tested the approach on cell types including fibroblasts and myoblasts and are now testing it on stem cells. A surprising and exciting finding was that we could treat the cells several times with enhanced effects on the capacity of cells to divide. For instance, after a first treatment, we saw an increase of 50,000-fold in cell numbers before cells stopped dividing, compared to untreated cells. If we waited a few weeks and repeated this treatment, we saw a similar gain in cell division and number. Since the increase in numbers is compounded with each treatment, a small sample of cells, for example from a small biopsy, can be amplified to very large numbers. (more…)