Horse

A horse, stem cells and an inspiring comeback story that may revolutionize tendon repair

/ Todd Dubnicoff / 2 Comments

Everyone loves a good comeback story. Probably because it leaves us feeling inspired and full of hope. But the comeback story about a horse named Dream Alliance may do more than that: his experience promises to help people with Achilles tendon injuries get fully healed and back on their feet more quickly.

Dream Alliance

Dream Alliance was bred and raised in a very poor Welsh town in the United Kingdom. One of the villagers had the dream of owning a thoroughbred racehorse. She convinced a group of her fellow townsfolk to pitch in $15 dollars a week to cover the costs of training the horse. Despite his lowly origins, Dream Alliance won his fourth race ever and his future looked bright. But during a race in 2008, one of his back hoofs cut a tendon in his front leg. The seemingly career-ending injury was so severe that the horse was nearly euthanized.

It works in horses, how about humans?
Instead, he received a novel stem cell procedure which healed the tendon and, incredibly, the thoroughbred went on to win the Welsh Grand National race 15 months later – one of the biggest races in the UK that is almost 4 miles long and involves jumping 22 fences. Researchers at the Royal Veterinary College in Liverpool developed the method and data gathered from the treatment of 1500 horses with this stem cell therapy show a 50% decrease in re-injury of the tendon.

It’s been so successful in horses that researchers at the University College of London and the Royal National Orthopaedic Hospital are currently running a clinical trial to test the procedure in humans.  Over the weekend, the Daily Mail ran a news story about the clinical trial. In it, team lead Andrew Goldberg explained how they got the human trial off the ground:

“Tendon injuries in horses are identical to those in humans, and using this evidence [from the 1500 treated horses] we were able to persuade the regulators to allow us to launch a small safety study in humans.”

Tendon repair: there’s got to be another way

Achilles tendon connects the calf muscle to the heel bone

The Achilles tendon is the largest tendon in the body and connects the calf muscle to the heel bone. It takes on a lot of strain during running and jumping so it’s a well-known injury to professional and recreational athletes but injuries also occur in those with a sedentary lifestyle. Altogether Achilles tendon injury occurs in about 5-10 people per 100,000. And about 25%-45% of those injuries require surgery which involves many months of crutches and it doesn’t always work. That’s why this stem cell approach is sorely needed.

The procedure is pretty straight forward as far as stem cell therapies go. Bone marrow from the patient’s hip is collected and mesenchymal stem cells – making up a small fraction of the marrow – are isolated. The stem cells are transferred to petri dishes and allowed to divide until there are several million cells. Then they are injected directly into the injured tendon.

A reason to be cautiously optimistic
Early results from the clinical trial are encouraging with a couple of the patients experiencing improvements. The Daily Mail article featured the clinical trial’s first patient who went from a very active lifestyle to one of excruciating ankle pain due to a gradually deteriorating Achilles tendon. Though hesitant when she first learned about the trial, the 46-year-old ultimately figured that the benefits outweighed the risk. That turned out to be a good decision:

“I worried, because no one had ever had it before, except a horse. But I was more worried I’d end up in a wheelchair. The difference now is amazing. I can do five miles on the treadmill without pain, and take my dog Honey on long walks again.”

The researchers aren’t exactly sure how the therapy works but mesenchymal stem cells are known to release factors that promote regeneration and reduce inflammation. The first patient’s positive results are just anecdotal at this point. The clinical trial is still recruiting volunteers so definitive results are still on the horizon. And even if that small trial is successful, larger clinical trials will be required to confirm effectiveness and safety. It will take time but without the careful gathering of this data, doctors and patients will remain in the dark about their chances for success with this stem cell treatment.

Hopefully the treatment proves to be successful and ushers in a golden era of comeback stories. Not just for star athletes eager to get back on the field but also for the average person whose career, good health and quality of life depends on their mobility.

Stem cell stories that caught our eye: Horse patients, Brain cancer stem cells, and a Bony Heart

/ Todd Dubnicoff / Leave a comment

Horsing around at the World Stem Cell Summit
The World Stem Cell Summit (WSCS) is coming up very shortly (December 6-9) in lovely downtown West Palm Beach, Florida. And this year it has an added attraction; horses.

For my money the WSCS is the most enjoyable of the many conferences held around the US focusing on stem cells. Most conferences have either scientists or patients and patient advocates. This brings them both together creating an event that highlights the science, the people doing it, and the people who hope to benefit from it.

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Eadweard Muybridge’s Galloping Horse
Image: Wikimedia Commons

And this year it’s not just about people, it’s also about horses. For the first time the event will feature the Equine World Stem Cell Summit. This makes sense on so many levels. Animals, large and small, have always been an important element in advancing scientific research, enabling us to test treatments and make sure they are safe before trying them out on people.

But horses are also athletes and sports has always been a powerful force in accelerating research. When you think about the “Sport of Kings” and how much money is involved in breeding and racing horses it’s not surprising that rich owners are always looking for new treatments that can help their thoroughbreds recover from injuries.

And if they help repair damaged bones and tendons in thoroughbreds, who’s to say those techniques and that research couldn’t help the rest of us.

Loss of gene allows cancer stem cells to invade the brain
A fundamental property of stem cells is their ability to self-renew and make unlimited copies of themselves. That ability is great for repairing the body but in the case of cancer stem cells, it is thought to be responsible for the uncontrolled, lethal growth of tumors.

Both stem cells and cancer stem cells rely on special cellular neighborhoods, or “niches”, to support their function. Outside of those niches, the cells don’t survive well. But cancer stem cells somehow overcome this barrier which allows them to spread and do damage to whole organs.

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Brain MRI showing glioblastoma tumor
Image: Wikimedia Commons

A study this week at The University of Texas MD Anderson Cancer Center zeroed in on the gene QK1 that, when deleted in mice, provides cancer stem cells in the brain the ability to thrive outside their niches.  They team also showed that the loss of the gene slowed a cell process called endocytosis, which normally acts to break down and recycle protein receptors on the cell surface. Those receptors are critical for the cancer stem cell’s self-renew function. So by blocking endocytosis, the gene deletion leads to an accumulation of receptors on the cell surface and in turn that boosts the cancer stem cells’ ability to divide and grow outside of its niche.

In a university press release picked up by Science Daily, team lead Jian Hu talked about exploiting this result to find new ways to defeat glioblastoma, the deadliest form of brain cancer:

“This study may lead to cancer therapeutic opportunities by targeting the mechanisms involved in maintaining cancer stem cells. Although loss of QKI allows glioma stem cells to thrive, it also renders certain vulnerabilities to the cancer cells. We hope to design new therapies to target these.”

CIRM-funded scientists uncover mystery of bone growth in the heart
Calcium helps keep our bones strong but a build-up of the mineral in our soft tissues, like the heart, is nothing but bad news for our health. The origins of this abnormal process called ectopic calcification have been a mystery to scientists because the cells responsible for forming bone and secreting calcium, called osteoblasts, are not found in the heart. So where is the calcium coming from?

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Bone-forming osteoblasts. They’re bad news when found in the heart.
Image: Amgen

This week, a CIRM-funded team at UCLA found the answer: cardiac fibroblasts. The researchers suspected that this most abundant cell in the heart was the culprit behind ectopic calcification. So, using some genetic engineering tricks, they were able to track cardiac fibroblasts with a red fluorescent tag inside mice after a heart injury.

Within a week or so after injury, the team observed that cardiac fibroblasts had clustered around the areas of calcium deposits in the heart. It turns out that those cardiac fibroblasts had taken on the properties of heart stem cells and then became bone-forming osteoblasts. To prove this finding, they took some of those cells and transplanted them into healthy mice. Sure enough, the injection sites where the cells were located began to accumulate calcium deposits.

A comparison of gene activity in these abnormal cells versus healthy cells identified a protein called EPPN1 whose levels were really elevated when these calcium deposits occurred. Blocking EPPN1 put a stop to the calcification in the heart. In a university press release, lead author Arjun Deb explained that this detective work may lead to long sought after therapies:

Everyone recognizes that calcification of the heart and blood vessels and kidneys is abnormal, but we haven’t had a single drug that can slow down or reverse calcification; our study points to some therapeutic targets.