Researchers have shown that injecting cardiac stem cells from young rats into the hearts of old rats can reverse the natural cardiac ageing process.

The study reflects potential that similar treatments could one day be used to prevent age-related heart function decline and cardiovascular disease in humans. As we get older the likelihood of developing cardiovascular disease increases, cell senescence underpins the cardiac ageing process. This is characterised by the shortening of telomeres, the end caps on our chromosomes. Telomere shortening is associated with heart dysfunction and hypertrophy, impaired cardiomyocyte proliferation, interstitial fibrosis, and reduced regenerative capacity.

In these latest animal studies, the researchers, from the Cedar-Sinai Heart Institute, tested whether cardiosphere-derived cells (CDCs) from newborn rates could reverse or hold back ageing in the hearts of old animals. CDCs are cardiac progenitor cells that can differentiate into the three primary cardiac cell types, including cardiomyocytes, endothelial cells, and smooth muscle cells.

The researchers injected the CDCs directly into the hearts of aged rats that had undergone echocardiogram testing, treadmill stress tests, and blood analyses at baseline. Equivalent tests were then carried out a month after the stem cell injections. The results of these and other analyses showed that the CDC treatment led to improved heart function and structure and boosted exercise capacity by about 20%.

The injections led to a range of non-cardiac specific effects, such as speeding hair growth, reducing systemic levels of inflammatory biomarkers, improving renal function, and helping to prevent weight loss secondary to cachexia or sarcopenia. Therefore, stem cell therapy was associated with lengthening in heart cell telomeres, resulting from activation of the enzyme tolemerase.

“Most of the CDC-related changes (85.5%) directionally recapitulated the gene expression patterns of young animals,” the authors explained in their published paper.

Leader of the study Eduardo Marbán, added, “The way the cells work to reverse ageing is fascinating. They secrete tiny vesicles that are chock-full of signalling molecules such as RNA and proteins. The vesicles from young cells appear to contain all the needed instructions to turn back the clock.”

Despite their progress, the researchers still don’t know whether stem cell therapy can extend life. Reaffirming this, Lilian Grigorian-Shamagian, co-primary investigator and the first author of the study, explained, “We have much to study, including whether the extracellular vesicles are able to reproduce all the rejuvenating effects we detect with CDCs.”

 

More on these topics