Stem Cell Transplantation Suppresses Cellular Senescence in Aging Rat Hearts

The usual model for presently available stem cell therapies is for stem cells to be taken from the patient, often from bone marrow, greatly expanded in number, and reintroduced into target tissues. This has been shown over the past decade to produce a wide range of benefits, with an increasing degree of confidence and reliability as techniques have improved. Stem cell transplants have been demonstrated to suppress inflammation, encourage greater regeneration on the part of native cell populations, and improve various other measures of tissue health. Different approaches and different stem cell types tend to produce a different mix of benefits. At this point some types of cell therapy are definitely more robust than others: stem cell treatments for joint issues and heart disease have a much greater expectation of benefits than, say, trying to treat autoimmune disorders or nerve damage.

Stem cell therapies are still under continued development. It is far from the case that every mechanism involved in the beneficial effects of stem cell transplantation is fully understood. A broad range of work is ongoing in many laboratories with the aim of creating a catalog of the effects of stem cell treatments, all of which feeds back into efforts to build better versions of existing cell therapies and introduce new therapies where none exist. An example of this sort of research is linked below: the researchers show that transplantation of mesenchymal stem cells reduces a few common measures of cellular senescence in rat hearts, both in cell culture and living animals. This may be important from the point of view of aging and age-related decline in tissue function. Senescent cells can no longer divide. They accumulate in damaged and old tissues, a defensive reaction that probably evolved to reduce cancer incidence by disabling replication in cells more likely to become cancerous. Unfortunately senescent cells emit all sorts of harmful molecular signals, and in large numbers they cause significant inflammation, tissue remodeling, and degradation of function. The presence of senescent cells is one of the contributing causes of degenerative aging.

It isn't clear from this research whether the use of stem cells produces any reversal of cellular senescence versus prevention of senescence only. By its definition senescence is an irreversible state of growth arrest, but there is a modest amount of evidence to suggest that at least some tissue types can cross the that line in both directions given the right stimulus.

Study Showing How Stem Cells Slow Aging May Lead to New Heart Failure Treatments

Aging is a complex and multifaceted process, resulting in damage to molecules, cells and tissue that in turn leads to declining organs. Mesenchymal stem cells, found in bone marrow, can generate bone, cartilage and fat cells that support the formation of blood and fibrous connective tissue. These stem cells also can be coaxed in the laboratory into becoming a variety of cell types, from cardiomyocytes (heart muscle cells) and neurons, to osteoblasts, smooth muscle cells, and more.

Several studies have already shown that MSCs can reverse age-related degeneration of multiple organs, restore physical and cognitive functions of aged mice, and improve age-associated osteoporosis, Parkinson's disease and atherosclerosis. "We previously showed that MSCs offer an anti-senescence action on cardiomyocytes as they grow older. However, what we didn't know was whether these findings from a cellular model could be applied to more physiological conditions in whole animals. That's what we wanted to learn with this study." They decided to explore their question using rats. After injecting MSCs into rat cardiomyoctyes being cultured in lab dishes and receiving encouraging results, they repeated the procedure on a group of young (4 months old) rats and old (20 months) rats, too. The results in both instances demonstrated that MSCs have a significant anti-aging effect.

Bone Marrow Mesenchymal Stem Cell Transplantation Retards the Natural Senescence of Rat Hearts

Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts. Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging hearts. Neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in the same dish with a semipermeable membrane to separate the two populations. Monocultured NRVCs displayed the senescence-associated phenotypes, characterized by an increase in the number of β-galactosidase-positive cells and decreases in the degradation and disappearance of cellular organelles in a time-dependent manner. The levels of reactive oxygen species and malondialdehyde were elevated, whereas the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased, along with upregulation of p53, p21Cip1/Waf1, and p16INK4a in the aging cardiomyocytes.

These deleterious alterations were abrogated in aging NRVCs cocultured with BMSCs. Qualitatively, the same senescent phenotypes were consistently observed in aging rat hearts. Notably, BMSC transplantation significantly prevented these detrimental alterations and improved the impaired cardiac function in the aging rats. In summary, BMSCs possess strong antisenescence action on the aging NRVCs and hearts and can improve cardiac function after transplantation in aging rats. The present study, therefore, provides an alternative approach for the treatment of heart failure in the elderly population.


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