The microenvironment around stem cells in aged tissue may serve as a major obstacle in the way of development or rejuvenation therapies. For example, old blood has a chemical composition that suppresses muscle stem cell replication and repair of old muscle tissue. Old senescent cells accelerate aging by their presence and senescent cells might create a microenvironment for other cells that suppresses their repair work. Now another research team finds evidence that old tissue contains more of a developmental protein that cause a reduction in stem cell supply.
Andrew Brack, PhD, of the MGH Center for Regenerative Medicine, senior and corresponding author of the Nature paper, says, "Just as it is important for athletes to build recovery time into their training schedules, stem cells also need time to recuperate, but we found that aged stem cells recuperate less often. We were surprised to find that the events prior to muscle regeneration had a major influence on regenerative potential. That makes sense to us as humans, in terms of the need to sleep and to eat a healthy diet, but that the need to rest also plays out at the level of stem cells is quite remarkable." An assistant professor of Medicine at Harvard Medical School, Brack is also a principal faculty member at the Harvard Stem Cell Institute.
Once we have the ability to create high quality stem cells of each type used by the body will they work when injected into various tissue types? Or will the proteins and other chemical compounds getting excreted from aging tissue suppress the stem cells and prevent them from doing repairs on the damage that accumulates in aging tissue? The protein FGF2 might be one of the obstacles on the road to aged tissue regeneration.
In a series of experiments in mice, the authors found that a developmental protein called fibroblast growth factor-2 (FGF2) is elevated in the aging muscle stem cell microenvironment and drives stem cells out of the dormant state. Satellite cells that are forced to replicate lose the ability to maintain their identity as stem cells, reducing the stem cell population."
Block FGF2 and get more muscle tissue repair.
The authors also found that blocking the age-related increase in FGF signaling both in aged satellite cells or in the cellular microenvironment protected against stem cell loss, maintained stem cell renewal during aging and dramatically improved the ability of aged muscle tissue to repair itself.
It might not be prudent to turn on old stem cells to divide more. The benefits of tissue repair have to be weighed against heightened risk of cancer that would come with turning up the rate at which stem cells divide. Though once we have great cures for cancer with minimal side effects the benefits of turning up replication in aged stem cells would probably outweigh the risks.
It may not be enough to just deliver youthful stem cells into aged tissue. We might also need the ability to manipulate the chemicals in the tissue environment so that stem cells will be free to do repair.
Lead author Joe Chakkalakal, PhD, a research fellow in Brack's lab, says, "This work highlights the usefulness of targeting the aged stem cell or its environment to protect stem cells and the tissues they serve from the effects of aging."