Fat is a rich source of stem cells for regenerative medicine. Treating someone with their own stem cells from their own fat certainly sounds like an attractive option. However, a new study shows that demonstrates that the therapeutic value of fat-based stem cells declines when those cells come from older patients.
“This could restrict the effectiveness of autologous cell therapy using fat, or adipose-derived mesenchymal stromal cells (ADSCs), and require that we test cell material before use and develop ways to pretreat ADSCs from aged patients to enhance their therapeutic potential,” said Anastasia Efimenko, M.D., Ph.D. Dr Efimenko and Nina Dzhoyashvili, M.D., were first authors of the study, which was led by Yelena Parfyonova, M.D., D.Sc., at Lomonosov Moscow State University, Moscow.
Heart disease remains the most common cause of death in most countries. Mesenchymal stromal cells (MSCs) collected from either bone marrow or fat are considered one of the most promising therapeutic agents for regenerating damaged tissue because of their ability to proliferate in culture and differentiate into different cell types. Even more importantly they also have the ability to stimulate the growth of new blood vessels (angiogenesis).
In particular, fat is considered an ideal source for MSCs because it is largely dispensable and the stem cells are easily accessible in large amounts with a minimally invasive procedure. ADSCs have been used in several clinical trials looking at cell therapy for heart conditions, but most of the studies used stem cells from relatively healthy young donors rather than sick, older ones, which are the typical patients who suffer from heart disease.
“We knew that aging and disease itself may negatively affect MSC activities,” Dr. Dzhoyashvili said. “So the aim of our study was to investigate how patient age affects the properties of ADSCs, with special emphasis on their ability to stimulate angiogenesis.”
The Russian team analyzed age-associated changes in ADSCs collected from patients of different age groups, including some patients who suffered from coronary artery disease and some without. The results showed that ADSCs from the older patients in both groups showed some of the characteristics of aging, including shorter telomeres (the caps on the ends of chromosomes that protect them from deterioration), which confirms that ADSCs do age.
“We showed that ADSCs from older patients both with and without coronary artery disease produced significantly less amounts of angiogenesis-stimulating factors compared with the younger patients in the study and their angiogenic capabilities lessened,” Dr. Efimenko concluded. “The results provide new insight into molecular mechanisms underlying the age-related decline of stem cells’ therapeutic potential.”
“These findings are significant because the successful development of cell therapies depends on a thorough understanding of how age may affect the regenerative potential of autologous cells,” said Anthony Atala, M.D., director of the Wake Forest Institute for Regenerative Medicine, and editor of STEM CELLS Translational Medicine, where this research was published.