The results of separate research into telomeres, human embryonic stem cells (hESCs) and related cellular mechanisms are starting to cross paths again. This is a good sign of progress - it shows that scientists understand these areas well enough to produce applications. In a press release from last week, Geron reports that they can use telomerase and limited control over embryonic stem cell differentiation to produce an immortalized growth medium from the stem cells under study:
In a report published in the November issue of the journal Stem Cells, scientists from Geron and the Roslin Institute demonstrated (i) that fibroblast-like cells could be differentiated from hESCs, (ii) that those cells could be immortalized with telomerase, and (iii) that the immortalized cells could then be used to produce conditioned medium to support feeder-free growth of undifferentiated hESCs.
hESCs are unique, unspecialized stem cells that can be grown in large quantities and differentiated into a wide variety of cell types potentially useful for treating a range of human diseases. Undifferentiated hESCs have unlimited proliferative capacity because they express the enzyme telomerase. In the course of differentiation, telomerase is down-regulated and the resulting differentiated cells have a finite lifespan. In these studies, the researchers derived fibroblast-like cells, termed HEF1 cells, from hESCs. The telomerase-negative HEF1 cells underwent senescence after approximately ten population doublings. Upon insertion of the gene encoding the catalytic subunit of telomerase in the HEF1 cells, the cells stably expressed high levels of telomerase activity, showed continuous growth in culture, and did not senesce. Moreover, the telomerase-immortalized HEF1 cells still responded to osteogenic inductive factors and were capable of differentiating into fully mature osteoblasts (bone-producing cells). These results show that cells derived from hESCs can be immortalized by insertion of the telomerase gene without affecting their ability to further differentiate into functional effector cells.
Geron has previously reported its development of an improved method for culturing hESCs in medium conditioned by mouse embryonic fibroblasts (MEFs), instead of on feeder layers of MEFs, thereby eliminating the need for direct contact with mouse cells. In the new studies, the telomerase-immortalized HEF1 cells were used to produce conditioned medium, which was shown to be capable of supporting the growth of undifferentiated hESCs, including the same hESC line from which the HEF1 cell was derived. The culture system was thus both human- rather than mouse-based, and genotypically homogeneous.
A little technical perhaps - but this is a noteworthy advance in the technologies that support cutting edge research into regenerative medicine. One of the show-stopping problems with many existing stem cell lines is that they are supported on mouse cells. This new advance will make the process of generating stem cell lines to order - in other words, tailored for work on a specific disease - that much easier.
In addition, this lends ammunition to calls for further research into the application of telomerase to extending the working life span of cell groups. You may recall that researchers recently did just this for immune system cells to prevent premature aging in HIV-positive patients.
"Immune cells that fight HIV are under constant strain to divide ... This massive amount of division shortens these cells' telomeres prematurely. So the telomeres of a 40-year-old person infected with HIV resemble those of a healthy 90-year-old person." This sort of premature aging is the result of a part of your body running at an accelerated rate - but with telomerase, "immune cells could divide endlessly. They grew at a normal rate and didn't show any chromosomal abnormalities that might lead to cancer."
So what else can we safely use telomerase for? This would seem to be a question worth spending time and money on.