Adult Skin
The British Broadcasting Corporation, BBC, reports that scientists are working on research that will expand the use of skin cells beyond skin grafts for burn victims that may be the answer for curing a broad range of conditions, from cancer to spinal cord repair.
Sheila MacNeil, Professor of Tissue Engineering at the University of Sheffield in South Yorkshire, England states, “There is the potential to take a biopsy of skin from a patient with disease, culture the cells, alter them to make them grow into tissues you are interested in and also use them to study the basis of the genetic disease and then to design therapies that you can put back into the patient.”
Professor MacNeil added that the adult stem cells were less likely to be rejected as they are from the donor’s own body, unlike stem cells from embryos.
The University of Sheffield is a leading research university and ranked 40th in the World’s Top 100 Universities by one study.
At Michigan State University’s Cellular Reprogramming Laboratory researchers are conducting studies on transforming ordinary skin cells into “anything” cells, known as pluripotent cells. The research team at the Laboratory takes adult human skin cells and converts them to a stem cell type known as Induced Pluripotent Stem Cells. They then grow these cells under conditions that push the cells to adopt a new identity as cells of specific types, such as neurons.
One of the benefits of using skin is that it is the largest organ of the body – adults carry around 8 pounds and 22 square feet of it.
With a simple, new technique, orthopaedic surgeons can now regenerate damaged cartilage in injured joints with stems cells harvested from their patients’ own blood.
AS she took the last steps to the top of Batu Caves, Joanna Hart was exhilarated. It was not something expected she could ever achieve at this point of her life, not when only two years ago, at age 34, she was offered an option usually given to people twice her age: a knee replacement for her left knee.
“Every time I go for X-rays, the radiologist look at the result and go, “‘Gosh, what happened to your knee? Your knee looked like a 70-year-old’s!’ It was very bad,” she described.
The medical history of her left knee was as extensive as it was active. Recurrent dislocations when she was 16 to 19 years old had resulted in a bad knee. “I was doing the high jump, long jump, relay, netball and hockey then. And so when I was 19 my kneecap dislocated – it wouldn’t stay in, it kept coming out,” she explained.
Her doctors recommended surgery to set her kneecap in the correct position to avoid it from dislocating further. However, it ended up giving her a different set of problems. The kneecap was set too high and it was rubbing against her bones.
“Over the years, all the cartilage got worn away,” she said. And as a result of that, bone spurs (osteophytes) started growing where her cartilage had worn off.
“As a midwife, I was very active. And I kept fracturing off those osteophytes and they got stuck in my joint,” she said. “And by then I wouldn’t be able to straighten or bend my leg because it’ll be locked. So, I had to go for surgery – they’ll pull the bit out, sew it up, and off I go again. This kept happening over a period of about 10 years.”
But being physically active in her line of work had kept her knee mobile. It was only when she stopped working that the spurs began building up in her joints again.
“Again, I couldn’t straighten my leg. So, I went to see a surgeon, who looked at the results of my arthroscopy (a minimally invasive surgical procedure to examine or treat a joint), and told me that I needed a total knee replacement,” she said.
As Hart was not keen on the idea, she hesitated – until she found another option that she could accept.
Stem cell repair
What Hart stumbled upon was a minimally invasive procedure, which was in its final stages of research in goats.
Using stem cells from goats, the doctors were able to stimulate cartilage regeneration in the goats’ knees.
“My quality of life was getting lesser by the day because at that point, after all the surgeries, I had to give up athletics, netball and hockey. And then I had to give up jogging and running,” Hart said.
However, what mattered most to her were not the activities she had to give up, but the life she was looking forward to with her children.
“I have two young children and I want to be able to go horse riding and skiing with them. A knee replacement is only going to stop the pain, but it would not make the restrictions any better.”
So, after the completion of animal studies (now accepted for publication in the Arthroscopy: The Journal of Arthroscopic and Related Surgery), Hart proceeded with the surgery. “Now I’m able to jog a little – more like shuffling, really – but I’m moving around a lot more, and I’m going for a skiing holiday this Christmas!” she said with a big grin.
“It’s really simple,” said orthopaedic surgeon Dr Saw Khay Yong, who led the research. “Once the diagnosis of cartilage injury is made, we then start with surgery where the patient has arthroscopy with subchondral drillings into the damaged cartilage areas.
“The stem cells are then harvested one week after surgery. It is a weekly injection into the knee joint starting at one week after surgery, for five consecutive weeks.”
Getting creative with old tools
“Peripheral blood stem cells (PBSCs) have been used by haematologists to treat leukemia patients for the last 20 years and subchondral drilling (the drilling of bone under cartilage layers) is also an established procedure in orthopaedics,” he said.
It all came together when Dr Saw and his colleagues, spurred by the desire to find another alternative to conventional methods of treating damaged cartilage, decided to give stem cells a try.
“If you look at cartilage injuries, currently there are a lot of possible solutions, but the results are inconsistent,” he said.
As some of the current options to treat damaged cartilage (autologous chondrocyte implantations, cartilage transfers and cartilage transplants) may be quite expensive and they often require multiple surgeries, they have never been attractive to him, Dr Saw said.
“So, we started to look into ways we can use stem cells to regenerate our cartilage with the University Veterinary Hospital at Universiti Putra Malaysia,” he added.
Their study in goats started in 2005, where Dr Saw’s team harvested stem cells from goat bone marrow and injected them into the goats’ knees after creating defects (by drilling holes in the cartilage and bone in their joints). When the study was completed in 2007, they proceeded to perform the procedure in humans.
What the procedure does is to accelerate the natural healing process that happens in articular (or hyaline) cartilages in the knee.
“Usually, when you have a partial thickness injury (when the cartilage wear has not exposed the underlying bone), there is no evidence of repair. But when you have a full thickness injury that penetrates into the bone, you can access the bone marrow stem cells within it, which will then initiate repair,” he explained.
By creating full thickness injuries by drilling holes in the bones where cartilage has worn out, you can create an environment where the cartilage can start to heal. And, to aid the process, doctors provide the building blocks: stem cells and hyaluronic acid (a chemical present in cartilage).
But how do the stem cells know where to go? Dr Saw explains: “When you drill the bone, it forms a blood clot. And when that happens, injured cells send out homing signals that attract stem cells from the bone marrow. After that, physiotherapy will provide the environment for the cells to grow into cartilage cells.
“And in this procedure, we provide the stem cells through injections,” he adds.
For the young and active
Although two-year results of the procedure in his patients are encouraging, Dr Saw is not recommending it for everyone.
As it takes a lot of physiotherapy and time – about two years – to achieve best results, he reckons that this might not be the best alternative for the elderly.
Former Miss Malaysia and model Betty Anne Brohier, 43, would attest to the challenges one has to face during recovery. A torn (and later removed) left meniscus (cartilage in the knee joint) when she was in her teens had stopped her from participating in sports but her job as a model has kept her on her feet (and heels) most of the time.
“It used to be quite painful but I thought it was fine. But throughout the years the pain became worse and it affected both knees,” she said.
Her left knee was on the verge of ”collapsing” when she finally agreed to undergo the procedure. “After the surgery, I stayed in the hospital for one week. Following that, for about six months, I used to go for physiotherapy three to four hours every day,” she said.
The road to recovery was long as she needed to learn how to walk and use her leg again. It took her six weeks after surgery to be able to move her leg. Another five months was spent moving around in crutches.
“No pain, no gain, I guess,” she pointed out.
Chip is a frisky, friendly 3-year-old chocolate Labrador. He’s also a cutting-edge laboratory experiment.
While the promise of stem-cell therapies remain largely unfulfilled for humans, they are succeeding in leaps and bounds in dogs like Chip, whose transplant for his elbow dysplasia did what drugs, physio, water therapy and two surgeries could not. Elbow dysplasia, common in certain dog breeds, is a condition involving multiple developmental abnormalities of the elbow-joint.
“It’s so exciting that they can do this,” says Toronto resident Anne Molloy, about the April transplant of her pet’s own stem cells.
Chip started limping at age 3 months, although he still loved to play and fetch, Molloy says. “You’d throw the stick for him and he’d start running, then buckle,” she says. “We could never take him on a walk. It was very sad.”
By a year his limp was bad enough that strangers constantly approached with concern and advice and he required a high dose anti-inflammatory and pain medication. After trying everything else, Molloy decided to try using her animal’s own ability to heal itself.
The therapy, by San Diego’s Vet-Stem, a company specializing in regenerative veterinary medicine, has been used successfully on horses since 2004 and dogs for the last 18 months.
About 3,500 horses and 2,000 dogs have been treated for hip and elbow dysplasia, osteoarthritis and tendon and ligament injuries, with success rates between 75 per cent and 95 per cent, according to survey results from veterinarians and owners, says company founder Bob Harman.
Here’s how it works:
While the animal is under general anesthetic, several tablespoons of fat are extracted from the abdomen or behind the shoulder, which is shipped overnight to the San Diego lab. That’s the worst part for the dog. On receipt of the fat, clinicians separate the stem cells from all other tissue, count the cells and divide them into proper doses within four hours, shipping one or two doses back to be injected into the joint the following day. The injection takes moments and is done under mild sedation.
Then magic seems to happen. The introduction of the stem cells to the injured joint signals anti-inflammatory cells and new blood cells to form.
It’s expensive – about $3,500 – but cheaper than joint replacement, which costs up to $10,000.
Some 2,000 veterinarians are certified to perform the procedure in the U.S., but there are fewer than 20 in Canada. Its launch here was six months ago in Halifax.
“In our clinic, we’re doing them almost every day, weekly certainly,” says Dr. Christine Zink, a veterinarian and professor at Johns Hopkins University School of Medicine in Baltimore, and an expert on canine agility. Other treatments have low efficacy, particularly compared to this, she says.
Most animals show reduced lameness, pain and swelling and increased range of motion within two weeks of the transplant, though improvement continues for up to six months.
That’s what happened to Chip, who perked right up, Molloy said.
Dr. Rona Sherebrin, of the Secord Animal Clinic, is the only vet certified by Vet-Stem in the GTA and practises at the clinic Molloy already attended.
“The fantastic thing about it is that it’s using the dog’s own tissue,” Sherebrin says, eliminating transplant complications and the need for immunosuppressive drugs.
Most fat extractions provide enough stem cells for four doses. The remaining ones are stored, frozen, at Vet-Stem, for the future, Harman says.
And future injections are usually necessary. The transplant works for about a year in most dogs, which means one extraction is usually enough for older dogs.
Some dogs can go longer, depending on their activity level, Sherebrin says.
The procedure doesn’t eliminate problems. Chip still needs some pain medication, but just a fraction of the high dose he required before. He also limps a little after hard play.
“If you’ve got a joint that’s abnormal and you heal it, it’s still got an abnormal shape and it’s still going to end up having more tendency to arthritic changes,” Sherebrin says.
The procedure is not approved in North America for people, although it’s in clinical trials in the U.S., Europe, Japan and Australia, Harman notes.
