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NOVEMBER 2017

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Stem Cells From Young Donors Could Combat Frailty in Old Age
 

Dave Roos 

 

Nov. 1, 2017 (Seeker.com) — Picture two 80-year-old women. One is confined to a wheelchair, physically weak, and wholly dependent on her family for buying food, getting around, and managing her finances. The second 80-year-old plays tennis every day and drives her own car. She’s physically active, mentally sharp, and 100-percent independent.

So what’s going on here? Both women have the same number of candles on their birthday cake, but they seem to be aging at different rates. The culprit, physicians say, is a condition called frailty that affects roughly 10 percent of all people over 60. Frailty is characterized by decreased physical function and immune response with age, but also cognitive loss and increasing dependence on others for daily tasks.

The good news is that while aging is inevitable, frailty can be staved off. The standard treatment regimens for frailty are exercise, better nutrition, and prescription drug management. But researchers from the University of Miami believe they may have found another solution: stem cells. In two separate trials, groups of people in their 70s suffering from moderate to severe frailty were injected with hundreds of millions of stem cells from young healthy donors. And the initial results were promising.

Dr. Joshua Hare is a professor of medicine and director of the Interdisciplinary Stem Cell Institute at the University of Miami, where he conducted both of the stem cell-frailty trials. Participants were run through a battery of physical and cognitive tests six months after receiving stem cell treatments, including a six-minute walking test on a treadmill.

“One of the most striking findings was the walk distance,” Hare told Seeker. “It was up about 60 to 70 meters, which is close to the length of a football field. That’s a big increase in walk distance in six minutes for a person who’s slowing down. That kind of difference can make a meaningful change in a person’s day-to-day experience.”

It’s been proven that all humans lose stem cells as we age. These adult stem cells reside in “niches” in our organs and bone marrow, and are responsible for replenishing dead cells and growing new ones. We need stem cells to grow hair, maintain organs, and heal wounds. All of this slows down as we age and our stem cell reserves are depleted.

But there’s one type of adult stem cell that serves as a “master regulator” of all other stem cells, Hare explained. Mesenchymal stem cells, which are found all over the body, including the lining of blood vessels, orchestrate the replenishing activity in tissue, organs, and bone marrow. Hare’s hypothesis was that by boosting the supply of these master stem cells in older people, it could replenish stem cells across the body and combat the symptoms of frailty.

Hare and his team started with bone marrow donations from healthy young individuals, extracted the mesenchymal stem cells, and then grew them out in a specialized on-campus lab. In the Phase I trial, the main goal was to prove that injecting subjects with mesenchymal stem cells was safe at various doses, from 50 million to 200 million individual cells.

For the 15 individuals who participated in Phase I, there were no negative immune responses or serious health effects (Okay, one subject passed away, but it was from unrelated causes).

As for positive outcomes, participants who received doses of the 100 million and 200 million stem cells experienced a 50 percent reduction in levels of an inflammatory biomarker called TNF-α, a signaling protein that’s been linked to mitochondrial dysfunction and disruption of organ systems. Lower levels of TNF-α means less inflammation, which is believed to be a driver of frailty.

The Phase II stem cell trial recruited more participants (30 people with frailty) and was a double-blind placebo-controlled study. Again, there were no negative health effects of the treatment, and participants receiving the 100 million stem cell dose showed the most physical and cognitive improvements. Inflammatory markers were down, quality-of-life scores were up, and there was even evidence that stem cell therapy strengthened immune response to infections, which usually weakens with aging.

Hare was quick to point out that while mesenchymal stem cells may be a promising treatment for frailty, the injections don’t represent a cure for aging.

“Anti-aging is a science fiction concept,” said Hare. “I don’t think we’re ever going to able to reverse aging. Frailty is aging at a faster rate. What I like about the frailty paradigm, it’s very biological, very definable, it’s very agreed upon. We’re all aging, and some people are aging in a negative way. This treatment could put them on a more positive trajectory.”

The goal of mesenchymal stem cell therapy isn’t necessarily to increase life span, Hare explained, but to increase “health span” — the number of years that an individual is healthy and active. What would be ideal, he said, would be to find a clear biomarker of frailty that could be measured and detected when a person is 60, so that stem cell or other anti-frailty treatments could be started as early as possible. Hare’s lab is actively searching for just such an early-detection system for frailty.

For now, the next step is to bump up the double-blind trials to 120 participants and further refine the dosage so that one day soon, that 80-year-old tennis player might have a doubles partner. 

 

 

 

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