Scientists rejuvenate old hearts by injecting younger stem cells

Injectable tissue patch could help repair damaged organs
Artificial blood vessels mimic rare accelerated ageing disease

Scientists have successfully reversed ageing in rats’ hearts – paving the way to a treatment for humans. Researchers at Cedars-Sinai Heart Institute, United States (US), injected fresh cardiac cells from newborn lab rats into old rats.

Previously, this experimental method has only been used as a way to repair damage after a heart attack.

But in this study, the Los Angeles-based team – who performed the world’s first cardiac stem cell infusion in 2009 – have demonstrated it can also reverse ageing.

Experts say the breakthrough could revolutionize medicine.

In the study, 22-month-old rats – who were considered old – received stem cells from four-month-old rats.

Across the board, all of them experienced improved heart function, improved their exercise capacity by an average of 20 percent, and regrew hair faster than rats that didn’t receive the cells.

They also demonstrated longer heart cell telomeres – compound structures located at the ends of chromosomes that shrink with age.

“Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions,” said lead author Dr. Eduardo Marbán, director of the Cedars-Sinai Heart Institute.

“Now we find that these specialized stem cells could turn out to reverse problems associated with ageing of the heart.”

Stem cells are a basic type of cell that can change into another type of more specialized cell through a process known as differentiation. Similar to a fresh ball of clay, they can be shaped and morphed into any cell in the body.

They grow in embryos as embryonic stem cells, used to help the rapidly growing baby form the millions of different cell types it needs to grow before birth.

Stem cells have been the focus of lots of medical research in recent decades because they can be used to grow almost any type of cell.

Marbán developed the process to grow cardiac-derived stem cells when he was on the faculty of Johns Hopkins University, and further developed it at Cedars-Sinai. In 2009, his team successfully repaired the damaged heart of a man who had suffered a heart attack, using his own heart tissue.

In the latest study, Marbán’s team injected cardiosphere-derived cells, a specific type of stem cell, from newborn laboratory rats into the hearts of rats with an average age of 22 months, which is considered aged.

Other laboratory rats from the same age group were assigned to receive placebo treatment, saline injections instead of stem cells. Both groups of aged rats were compared to a group of young rats with an average age of four months. Baseline heart function was measured in all rats, using echocardiograms, treadmill stress tests and blood analysis. The group of older rats underwent an additional round of testing one month after receiving cardiosphere-derived cells that came from young rats.

This experimental method has only been used as a way to repair damage after a heart attack

The team is also studying the use of stem cells to treat patients with Duchenne muscular dystrophy, and patients with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients.

Also, a team of U of T Engineering researchers is mending broken hearts with an expanding tissue bandage a little smaller than a postage stamp.

Repairing heart tissue destroyed by a heart attack or medical condition with regenerative cells or tissues usually requires invasive open-heart surgery. But now biomedical engineering Professor Milica Radisic and her colleagues have developed a technique that lets them use a small needle to inject a repair patch, without the need to open up the chest cavity.

The research was published in Nature Materials.

Radisic’s team are experts in using polymer scaffolds to grow realistic 3D slices of human tissue in the lab. One of their creations, AngioChip, is a tiny patch of heart tissue with its own blood vessels — the heart cells even beat with a regular rhythm. Another one of their innovations snaps together like sheets of Velcro™.

Such lab-grown tissues are already being used to test potential drug candidates for side effects, but the long-term goal is to implant them back into the body to repair damage.

After dozens of attempts, Montgomery found a design that matched the mechanical properties of the target tissue, and had the required shape-memory behaviour: as it emerges from the needle, the patch unfolds itself into a bandage-like shape.

The next step was to seed the patch with real heart cells. After letting them grow for a few days, they injected the patch into rats and pigs. Not only does the injected patch unfold to nearly the same size as a patch implanted by more invasive methods, the heart cells survive the procedure well.

The scaffold is built out of the same biocompatible, biodegradable polymer used in the team’s previous creations. Over time, the scaffold will naturally break down, leaving behind the new tissue.

The team also showed that injecting the patch into rat hearts can improve cardiac function after a heart attack: damaged ventricles pumped more blood than they did without the patch.

There is still a long way to go before the material is ready for clinical trials. Radisic and her team are collaborating with researchers at the Hospital for Sick Children to assess the long-term stability of the patches, as well as whether the improved cardiac function can be maintained.

They have also applied for patents on the invention and are exploring the use of the patch in other organs, such as the liver.

Also, biomedical engineers have grown miniature human blood vessels that exhibit many of the symptoms and drug reactions associated with Hutchinson-Gilford Progeria Syndrome — an extremely rare genetic disease that causes symptoms resembling accelerated aging in children.

The technology will help doctors and researchers screen potential therapeutics for the disease more rapidly, with the goal of eventually creating a platform for personalized screening. The technique also offers a new way to study other rare diseases and could provide insights into treating heart disease in the elderly.

The study was published online on August 15 in the journal Scientific Reports.

“One of the drugs currently prescribed for this disease extends patients’ lives by three months, and that’s been considered a major feat,” said Leigh Atchison, a doctoral candidate in biomedical engineering at Duke University and first author of the study. “They’re looking for anything that will extend lifespan by even a few months. It’s that devastating.”

Hutchinson-Gilford Progeria Syndrome — or simply progeria for short — is a non-hereditary genetic disease caused by a single-point mutation in the genome. It is so rare and so deadly that there are currently only about 250 known cases worldwide.

Progeria is triggered by a defective protein called progerin that accumulates outside of a cell’s nucleus rather than becoming part of its structural support system. This causes the nucleus to take on an abnormal shape and inhibits its ability to divide. The resulting symptoms look much like accelerated aging, and affected patients usually die of heart disease brought on by weakened blood vessels before the age of 14.

The research may also provide insight into why some elderly people become especially prone to heart disease. Many heart patients have shown the same buildup of the progerin protein, so researchers believe there may be a link between the two conditions.

There are, of course, limitations to the new artificial blood vessels. They are not connected to any outside organs, nor are they embedded in the complicated biology of a living human being.