A new study released today in STEM CELLS Translational Medicine demonstrates that the therapeutic value of stem cells collected from fat declines when the 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. She and Nina Dzhoyashvili, M.D., were first authors of the study led by Yelena Parfyonova, M.D., D.Sc., at Lomonosov Moscow State University, Moscow.
Cardiovascular disease remains the most common cause of death in most countries. Mesenchymal stromal cells (MSCs), stem cells collected from either bone marrow or adipose tissue, are considered one of the most promising therapeutic agents for regenerating damaged tissue because of their proliferation potential and ability to be coaxed into different cell types. Importantly, they also have the ability to stimulate the growth of new blood vessels, a process known as angiogenesis.
Adipose tissue in particular is considered an ideal source for MSCs because it is largely dispensable and the stem cells are easily accessible in large amounts using a minimally invasive procedure. ADSCs have been used in several clinical trials looking at cell therapy for heart conditions, but most of the studies employed cells taken from relatively healthy young donors rather than sick, older ones - the typical patient when it comes to 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 team analyzed age-associated changes in ADSCs collected from patients of different age groups, including some with coronary artery disease and some without. The results showed that ADSCs from the older patients in both groups expressed various age markers, including shorter telomeres, and, thus, confirmed that ADSCs did age. Telomeres, the regions of repetitive DNA at the end of a chromosome, protect it from deterioration.
"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., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.