New stem cell studies at the University of Maryland Dental School demonstrate that surgeons could one day routinely use strong, mold-able, and inject-able pastes to regenerate needed bone tissue to repair broken bones, fractures, genetic defects, even combat bone wounds.
The Dental School’s Huakun Xu, PhD, MS; Michael Weir, PhD, MS; and Ryan Zhao, MD, PhD, presented their findings today at the World Stem Cell Summit at the Baltimore Convention Center before hundreds of stem cell experts from 25 countries.
The Dental School presentation showed that human stem cells seeded in a tissue engineering scaffolding exhibited “excellent attachment and osteogenic differentiation,” which is the process of laying down new bone material.
The researchers said the new findings buoy hopes that an inject-able paste of stem cells will be available one day to fill any shape of cavity from bone defects, breaks or wounds by regenerating needed bone tissue.
In test tube studies, stem cells from bone marrow, when placed into an inject-able scaffold of calcium phosphate and chitosan, started growing and forming minerals needed for new bone tissue.
Xu, an associate professor, is the principal investigator of a $230,000 grant from the Maryland Stem Cell Research Fund for “Stem Cell Delivery via Inject-able, Nano-apatite Scaffolds for Bone Engineering,” and a $1.84 million grant from the National Institute of Dental and Craniofacial Research.
The Dental School researchers have so far tested four scaffolding materials for gripping and holding the stem cells. “Which of the materials will be used in a commercial product really depends on where you want to place the material, whether in the jaw bone, the cranium or other bones,” said Weir, a research assistant professor.
Weir said, “Ultimately we want this to be an inject-able paste so we can put it into voids that are not square, rectangular or circular, that they are irregular shapes that need to be filled. The paste will include the cells.”
Xu added that such a product could also be used in periodontal bone repair, mandibular and maxillary ridge augmentation, reconstruction of frontal sinus and craniofacial skeletal defects, and other stress-bearing orthopedic applications. After a tumor removal or traffic accident, there may be a need to repair the damage or void left. It will beneficial, he said, to have a paste that can be shaped easily to achieve a high degree of aesthetics. After shaping, the paste hardens to form a solid scaffold full of pores and channels and still containing stem cells throughout, still living and growing to form new bone. Eventually the scaffold material degrades and is replaced entirely by new bone tissue grown from the stem cells.
The researchers found that a significant number of the cells were alive after a few weeks in the scaffolding material. They then discovered that the cells were differentiating into osteoblasts, essentially turning into bone cells. (From Greek words for bone, an osteoblast cell is responsible for bone formation.)
After staining the scaffold, the researchers found the osteoblasts forming “a lot” of the mineral, which then forms the bone after only 21 days, said Weir. In a subsequent experiment, the cells survived even better when mixed in a gel of the scaffolding material.
The researchers have recorded similar success with umbilical cord-derived stem cells, which “appear to be more potent in terms of growth and transforming into osteoblasts on the scaffold than the cells from bone marrow,” said Xu. It is likely that the umbilical cord cells are more vital because they are younger than stem cells obtained from the adult bone marrow and in theory will act more quickly to repair wounds or bone defects.
Xu explained: “When a 16-year-old breaks a bone, it usually takes a few weeks to heal. In a 60-year-old, it likely takes a few months. Umbilical cord stem cells are only 9 months old and hence are fast in healing.” Xu said human umbilical cord stem cells have the promise to be a superior alternative to bone marrow-derived stem cells, the latter requiring an invasive procedure to harvest. For combat medics, the umbilical cord derived stem cells could potentially be on the shelf and used in the field without causing immunuorejection, said Xu.
Xu said that after a literature search, he believes his laboratory is the first to investigate the seeding of umbilical cord-derived stem cells in injectable and load-bearing scaffolding for bone tissue engineering.
“We are excited about the promise of encapsulating umbilical cord stem cells in an injectable scaffold for stem cell delivery and bone regeneration.” Xu said. “Our research is still in an early stage. We will perform more systematic investigations and animal studies. If indeed human umbilical cord stem cells delivered using injectable scaffolds are more effective in bone regeneration than the commonly studied bone marrow stem cells, it will broadly impact the field of stem cell-based regenerative medicine.”
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.
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.
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Nostrils flaring, ears pricked, Solid Gold shifted nervously as the vet stroked his injured foreleg.
The three-year-old racehorse had no way of knowing this injection would save his career, not end it.
While debate rages over the ethics of stem cell research for humans, a Singapore-based firm has given Asian racehorse owners a new weapon in the battle against career-threatening tendon and ligament injuries.
After harvesting bone marrow from the horse’s sternum, EZ Stemcell separates multi-potential stem cells, which are then injected directly into the injured tendon.
This cutting-edge technology will not only revolutionise the way injured horses are treated, says Dr Omie Rangabashyam, but two-legged patients could one day be treated in a similar way.
“By injecting the stem cells directly into the core lesion, the tendon will regain its integrity, will regain its strength, without the fibrous scar tissue that forms with conventional treatment,” Rangabashyam, a director of EZ Stemcell, told Reuters as he tried to calm the horse.
“Without stem cell therapy, Solid Gold would have been rested for a year, raced again and the tendon would probably tear again.
“That would be the end of him.”
COOL CURED
Following a few days’ box rest, Solid Gold will undergo a programme of gentle walks and exercise to get the tendon working as normal. He should be doing solid work on the track in about seven months, said Rangabashyam.
The treatment has already been used in Britain to some success, with the Martin Pipe-trained Mr Cool receiving stem cell therapy after injuring a tendon in March 2004.
The hurdler returned to competitive racing a year later and went on to win on its second outing after the procedure.
EZ Stemcell had already been approached by owners throughout Asia and Australia and the firm was looking into the possibility of expanding into the lucrative Dubai racing scene.
For owners and trainers in Singapore, where the racing calendar peaks with the $3 million Singapore Airlines International Cup, counting the cost of injuries runs into millions of dollars.
Rangabashyam, who owns more than 30 horses stabled at the Singapore Turf Club, paid 500,000 Singapore dollars ($308,600) for a German horse that has since run just twice in 2 ¸ years because of a succession of injuries.
A stem cell shot costs 2,888 Singapore dollars.
Mark Clements was the first trainer in Singapore to have a horse treated with stem cells.
“The traditional way to treat a horse with a tendon problem was rest — throw it in the stable and forget about it for a year,” the Zimbabwe native told Reuters at the Turf Club.
“They were also injecting various drugs into the injury, which never really worked.
“They had limited success with injecting raw bone marrow but the results with stem cells are on a different level.
“No scar tissue means the tendon gets its elasticity back, which means the horse’s movement, and ultimately its speed, is virtually unaffected.”
ENDLESS POSSIBILITIES
The benefits of stem cell therapy may one day reach far beyond racing circles.
Doctors in Thailand have been using an experimental procedure to treat heart patients with adult stem cells harvested from their own blood, bypassing both the risk of rejection and the controversial subject of embryonic stem cell use.
Some people oppose the use of embryonic stem cells, saying a human life must be destroyed to grow the cells.
Companies in the United States are also exploring the commercial potential for stem cells as treatment for diseases such as diabetes.
Rangabashyam, a liver specialist at Singapore’s Gleneagles hospital, says the green light for using stem cells in the treatment of liver disease is not far off.
“Soon we’ll have it for acute liver disease, for acute renal disease. There’s trials going on in the U.S. for the treatment of neurological disease,” he added.
Another Singapore firm was storing umbilical cords of newborns so that they could perhaps one day be used to cure them of disease or injury.
“The physiology of all living things is the same. With stem cells, anything is possible.”
Researchers at a Children’s Hospital in Oakland believe they have found a new source of stem cells that could cure a variety of blood diseases. The breakthrough would help not just children, but adults as well.
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Researchers took stem cells from the placentas of consenting women who had Ceasarian sections at Alta Bates Medical Center in Berkeley. Doctors found a large number of blood producing stem cells in those organs which they were able to grow.
Researchers say these cells don’t have to perfectly match the bone marrow of patients looking for transplants.
“The important thing is can you harvest them, are there plenty of them and can you use them? And that’s what we have shown,” said Dr. Frans Keypers.
Patients currently have to wait until a bone marrow donor match is found and if the tissue isn’t similar, the body will reject the transplanted marrow. With these placental stem cells, the match doesn’t have to be as precise, offering hope to African American, Asian and multiracial patients who often can’t find donor matches.
Before this, scientists were primarily studying embryonic stem cells which have the ability to grow into any kind of cell type. The findings appear in the next month’s issue of Experimental Biology and Medicine.
Stempeutics Research Pvt Ltd, a group company of Manipal Group, has achieved a major breakthrough in stem cell production technology with the manufacture of its Investigational New drug (IND) sourced from Mesenchymal Stem Cells (MSCs) derived from bone marrow of healthy donors. Using the IND, the company has commenced the placebo controlled double blind trials at Bangalore, Kochi, Hyderabad, Ahmedabad and New Delhi.
The company through its newly designed proprietary technology is able to achieve large scale expansion of MSCs at its cGMP compliant unit at Manipal near Mangalore. It can produce stem cell-based drugs for over 10,000 patients from a single healthy donor through the innovative technology. MSC has received considerable attention in biological research because of its self renewal capability and its ability to expand and trans-differentiate into many different cell lineages. In addition, MSCs are immune privileged and there are no ethical issues involved since it is derived from adult stem cells. To meet large scale bio-production and make the drug affordable, a fast MSCs expansion method was the need of the hour, BN Manohar, president, Stempeutics Research stated.
Having gathered information about the path breaking research and production efforts, Union minister for state science and technology, Prithviraj Chavan who was in Bangalore made a surprise call at the company to have a first hand comprehension of the development.
“Taking into consideration, the lack of a uniform approach for MSC culture and expansion, we designed a technology and manufacturing process by identifying an optimal culture media and the harvesting time. We also ensured an appropriate combination of cell culture containers – while maintaining its multi-lineage differentiation potential. Through this production research which has lasted for more than two years, Stempeutics has achieved its break through where by it can produce from a healthy voluntary donor, drugs required for more than 10,000 patients,” explained Manohar.
According to Dr Ranjan Pai, MD & CEO, Manipal Education & Medical Group, the global market for Stem Cell therapies estimated US$20 billion by 2010. Adult Stem Cell therapy currently dominates the global stem cells market with a share of almost 58 percent. The current stem cell therapy market in India is valued around US$540 million. While the opportunity is good it is essential that cost of stem cell treatment becomes less so that it is affordable by a common man. It is essential to come out with innovative production techniques for up scaling and make therapy affordable, he added.
Researchers are suggesting that discarded fallopian tubes from hysterectomies could be a good source of donor stem cells — offering another “ethical” route to creating stem cell treatments without using embryos, BBC News reported.
Experts say they contain a rich source of the immature cells that have the potential to become a variety of the body’s tissues, like muscle and bone.
Previous studies have shown it is possible to get mesenchymal stem cells from umbilical cords, menstrual blood, teeth and fat tissue.
University of São Paulo researchers now believe that fallopian tubes, discarded during the course of hysterectomies or female sterilization operations, may also have an abundant source of these cells.
The scientists were able to harvest, multiply and then coax the mesenchymal stem cells to turn into healthy muscle, fat, cartilage and bone cell lines in the lab, according to the findings published in The Journal of Translational Medicine.
The team suggests these adult stem cells could also be useful for understanding and treating fertility problems since they are capable of replacing damaged cells in the fallopian tube.
While these cells could provide a source of stem cells for regenerative medicine, it will still take more time and research before they could be given to patients, the team noted.
Since stem cells from embryos are in a so-called pluripotent state, meaning they have an unlimited capacity to become any of the types of cells and tissue in the human body, most of the work on stem cells has focused on that type of research.
However, many religious groups and objectors argue it is unethical to destroy embryos in the name of science.
“This is another promising source to add to the list of so-called ‘ethical’ sources of stem cells,” said stem cell expert Stephen Minger of Kings College London.
But Minger noted that bone marrow and fat were more accessible and less intrusive sources for stem cells.
“Obtaining multi-potent stem cells from discarded fallopian tubes is yet another example of the extraordinary potential of human waste tissue,” said Josephine Quintavalle of Comment on Reproductive Ethics.
She hopes that these cells could also be used for infertility problems in women, as they could possibly repair damaged fallopian tubes for women who can’t conceive.
Amid the blast walls and cacophony of Baghdad, patients at a local clinic are receiving potentially groundbreaking stem cell therapy, treatments that remain illegal and unproven in many countries.
Dr. Abdul Majeed Alwan Hammadi is conducting the treatments for free, mostly on young Iraqis. He is a clinical hematologist who works in the Bone Marrow Transplant Center, part of Baghdad’s Medical City complex of hospitals on the eastern banks of the Tigris River.
Hammadi says he started therapies in 2008 and has so far treated 34 patients, the majority for multiple sclerosis.
Bagdad Iraq
Hammadi, who graduated from a medical college in Baghdad, claims no side effects have been reported in his patients. He said he is in the process of collecting his data for publication, while also seeking official license for the therapies from Iraq’s Ministry of Health, which funds the center.
One of Hammadi’s patients and proponents of the therapy is the Rev. Andrew White, a British priest who runs St. George Church on Baghdad’s Haifa Street.
White was diagnosed with multiple sclerosis in 1998 and said his vision, speech and motor skills were steadily degenerating until he began Hammadi’s therapy in January.
White helped Hammadi establish the bone marrow center in Baghdad in 2001, bringing the doctor and his staff to England for training in marrow transplant techniques.
White said his slurred speech and other MS symptoms improved since starting the three-hour therapy sessions, which involves Hammadi extracting adult stem cells from White’s blood and then injecting them into his spinal cord.
It is unknown why MS causes the body’s immune system to attack the protective coating around nerve fibers, known as myelin, which results in nerve damage and loss of motor functions. The condition’s severity varies, with some people improving on their own while others continue to degenerate.
The potential benefits of stem cell therapy for MS are still being analyzed and researched in the Western world, but White said he accepted Hammadi’s offer for treatment because his symptoms were so severe and he trusted his friend.
“When there’s no other treatment, you kind of just go with it,” White said. “At least there’s a chance.”
White said the therapy itself “can be a bit painful” since it involves a spinal cord puncture, but there has been a “massive difference” in his condition.
“It’s very rare for me to actually feel ill now,” he said. “My balance is still quite bad and my vision is not perfect, but I do not feel ill.”
MS doctors and researchers believe stem cell therapies could pose benefits for those suffering from the disease, but the research is still unproven at this point, according to Dr. Patricia O’Looney, vice president of biomedical research for the National Multiple Sclerosis Society’s research and clinical program department.
One theory is that a person’s adult stem cells can work to rebuild the myelin around nerve fibers that is eaten away by a person’s immune system under MS, halting any further damage.
Hammadi said he is the only doctor in Iraq performing such therapies, but that there are similar operations being performed in Iran and Lebanon.
At this point, the therapies aren’t proven, and any side effects from the treatments are unknown, O’Looney said. “We’re seeing a wide range of results [at the stem cell clinics], which tells us there might be a hint of benefit, but what we need to do of course is a larger study to really understand if stem cell therapy is beneficial,” she said, adding that because stem cell research is only about 10 years old, enough isn’t known yet about the cells. “We do discourage anyone with MS from going to these so-called stem cell clinics,” O’Looney said.
But for patients like White and others suffering from the disease, waiting for the research to come through can be too much to bear.
Part of some patients’ sense of urgency comes from the disease’s unpredictability. Sometimes the disease goes into remission on its own; sometimes a patient is in a wheelchair within 10 years of being diagnosed.
As a result, MS sufferers have sought out a variety of cures over the years, O’Looney said. “If you flash back 25 years ago before [current MS therapies], people were using snake venom or bee stings.”
Stem cell clinics based on untested science can also give false hope to those with MS, O’Looney said, and positive results like White’s could be due to a number of factors, from pre-existing therapy regimens to the body’s immune system correcting itself on its own. “Just because someone switched from tomato juice to orange juice in the morning and feels better doesn’t mean it’s the orange juice,” she said. “The body does have the capability to repair itself.”
But for some patients like White, hope is all there is when dealing with MS. No matter where the treatment takes place.
“In the midst of the war zone, I get such high-tech treatment,” he said. “I can go to Baghdad and get it.”
According to a new report in Fortune Magazine, marketable therapies emerging from work in the (less controversial) adult stem space could be the next multi-billion dollar market.
Research on adult stem cells has generated a great deal of excitement. Adult stem cells have already been used successfully with patients: to treat cartilage defects in children; restore vision to patients who were legally blind; relieve systemic lupus, multiple sclerosis, and rheumatoid arthritis; and to serve as an aid in numerous cancer treatments.
Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for 40 years. Scientists now have evidence that stem cells exist in the brain and the heart. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies. These Adult stem cells can be harvested from many areas of the body, including the bone marrow, fat and peripheral blood. Once the cells have been harvested, they are sent to the lab where they are purified and assessed for quality before being reintroduced back in the patient. Since the stem cells come from the patient there is no possibility for rejection and they are used in transplants to treat diseases, such as cancers like leukemia.
According to various studies, stem cells isolated from a patient (i.e. from the bone marrow or fat) have the ability to become different cell types (i.e. nerve cells, liver cells, heart cells and cartilage cells). Studies have also shown that these are capable of “homing in” on and repairing damaged tissue. Researchers feel they are far closer to commercializing drugs based on adult stem cells than any product based on embryonic stem cells. In fact, many clinics outside of North America already tout stem cell based treatments to treat chronic diseases for which there are inadequate standard therapies. These clinics currently accept patients with Diabetes Type 2, Autoimmune Diseases, Multiple Sclerosis, Degenerative Joint Disease, Autoimmune Diseases as well as Rheumatoid Arthritis and Osteoarthritis. Unfortunately, patients seeking those treatments in other countries most often run the risk of parting with their money and being disappointed with the results.
Back in the states, Robin Young, a medical industry analyst from RRY Publications, estimates that gross sales of adult cellular therapies will be well over $100 million this year. By 2018, he says stem cell therapy revenues could grow to $8.2 billion.
“Adult derived cells are the ones that have been studied for the past 10 to 15 years and are ready for prime time,” says Debra Grega, the executive director of the Center for Stem Cell and Regenerative Medicine at Case Western Reserve University. “Large pharmaceutical companies are now wanting to get into the adult stem cell therapeutic area. That indicates to me that there is enough safety and enough efficacy that they are willing to put money in.”
Pharmaceutical giant Pfizer (NYSE:PFE) announced in November that it would invest up to $100 million in regenerative research, which would include both adult and embryonic stem cell research, over a three to five year period.
The overall stem cell market, however, is still quite small. The California-based outfit Geron (NASDAQ:GERN) dominates the embryonic stem cell market, and is perhaps 10 years away from commercializing a spinal cord treatment based on its research.
The frontrunner in the adult stem cell space, according to Forbes, is Osiris Therapeutics, Inc.(NASDAQ:OSIR)- currently trading at $14.20 per share. Genzyme Corp. (NASDAQ:GENZ) has signed a partnership alliance with Osiris Therapeutics to develop two late-stage adult stem cell treatments — Prochymal and Chondrogen — thought to be useful to treat a variety of diseases by controlling inflammation, promoting growth of new tissue and preventing scars. The deal will pay Osiris $130 million upfront ($75 million initially and the difference to be paid on July 1, 2009). Assuming the drugs reach the marketplace, Genzyme will pay up to $1.25 billion in development, regulatory and sales milestone payments.
Osiris is focused on developing and marketing products to treat medical conditions in the inflammatory, orthopedic, and cardiovascular areas. Their principal biologic drug candidate, Prochymal, is being evaluated in Phase III clinical trials for three indications, including acute and steroid refractory Graft versus Host Disease (GvHD), Crohn’s disease and for the repair of gastrointestinal injury resulting from radiation exposure, and is the only stem cell therapeutic granted both Orphan Drug and Fast Track status by the United States Food and Drug Administration (FDA). Prochymal is also being developed for the repair of heart tissue following a heart attack, for protection of pancreatic islet cells in patients with type I diabetes, and for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The FDA could approve within a year which fights a painful illness called “graft-versus-host disease” which afflicts transplant recipients. If they succeed, Osiris would be the first company to gain approval for a stem cell drug. Osiris will commercialize both drugs in the U.S. and Canada, and Genzyme will sell the drugs in all other countries.
Investors should be aware that there are only a limited number of stocks which are pure plays or semi-pure plays in the stem cell industry. Below are some of the companies working in the adult stem cell medicine space:
StemCells, Inc.(NASDAQ:STEM) – a company is engaged in the discovery and development of cell-based therapeutics to treat damage to, or degeneration of, major organ systems. Currently trading at $1.60 with a market cap of $164.09M.
Cytori Therapeutics Inc. (NASDAQ:CYTX) which develops, manufactures, and sells medical technologies to enable the practice of regenerative medicine. The Company’s commercial activities are focused on cosmetic and reconstructive surgery in Europe and Asia-Pacific, and stem and regenerative cell banking (cell preservation) in worldwide. Its product pipeline includes the development of new treatments for cardiovascular disease, spinal disc degeneration, gastrointestinal disorders, liver and renal disease and pelvic health conditions. They currently trade at $3.55 with a market cap of $121.02M.
Aastrom Biosciences, Inc.(NASDAQ:ASTM) engaged in the development of autologous cell products for the repair or regeneration of human tissue. The Company’s tissue repair cell (TRC) technology involves the use of a patient’s own cells to manufacture products to treat a range of chronic diseases and serious injuries affecting vascular, bone, cardiac and neural tissues. Aastrom’s TRC-based products contain increased numbers of stem and early progenitor cells, produced from a small amount of bone marrow collected from the patient. Late last month, the company made headlines after temporarily suspending enrollment and patient treatment in its U.S. Phase II IMPACT-DCM clinical trial following a report that a patient died at home after being released from the hospital following treatment in the trial. The stock trades at $0.36 pps with a market cap of $58.44M.
ThermoGenesis Corp.(NASDAQ:KOOL) designs, manufactures and markets automated and semi-automated devices and single-use processing disposables that enable hospitals and blood banks to manufacture a therapeutic dose of stem cells, wound healing proteins or growth factors from a single unit of cord blood or the patient’s own blood in less than one hour. They currently trade at just under $0.70 and have a market cap of $37.02M.
Opexa Therapeutics, Inc. (Nasdaq:OPEXA) is a biopharmaceutical company developing autologous cellular therapies with the potential to treat major illnesses, including multiple sclerosis (MS) and diabetes. The Company has a global license from Baylor College of Medicine (or Baylor) to an individualized T-cell therapeutic vaccine, Tovaxin, which is in clinical development for the treatment of MS. MS is the result of a person’s own T-cells attacking the myelin sheath that coats the nerve cells of the central nervous system (CNS). Shares currently trade under $0.60 with a market cap of $7.29M.
The human placenta could be an important source of stem cells for curing leukemia, sickle cell disease and other blood-related disorders, a new study reveals.
These stem cells appear to have distinct advantages over the techniques currently used to fight such diseases, and they may one day provide an alternative treatment for people who cannot find matching bone marrow donors, researchers said.
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Scientists at Children’s Hospital Oakland obtained placentas from consenting women who had cesarean sections at Alta Bates Summit Medical Center in Berkeley.
They found that the placentas contained large numbers of blood-producing stem cells, which they were able to remove and grow in a cell culture.
“Yes, the potential is there,” said senior scientist Frans Kuypers. “Yes, you can get them out, and yes, they’re viable.”
One big advantage of such stem cells is that they do not require the perfect match needed for those who have bone marrow transplants, Kuypers said, because they do not trigger the same strong immune system response.
Today, scientists often seek to cure people who have leukemia and other blood-related disorders by giving them stem cell-rich bone marrow from donors who have closely matched tissue types. The transplanted bone marrow makes healthy blood cells to replace the faulty ones.
But if the donor has a different tissue type, the recipient’s body will not recognize the new cells and
will attack them, leading to what is known as graft-versus-host disease.The placental stem cells, like umbilical cord blood, “are much more tolerant with respect to matching,” Kuypers said.
The findings, which will appear in the July issue of Experimental Biology and Medicine, could represent especially good news for African-Americans, Asians and multiracial individuals, who often have difficulty obtaining compatible bone marrow donors.
“Many minorities cannot find a match in the national donor program, and as a consequence of that, they may die,” said Dr. Bert Lubin, senior vice president of research for Children’s Hospital.
Despite the hopeful signs of placental stem cells, their widespread use is probably several years away. Children’s Hospital will seek to raise the money to do clinical trials in humans.
The study serves as an important reminder that research in California should not focus solely on embryonic stem cells, which have the ability to transform into any cell type, said Hanna Mikkola, a researcher with the Broad Stem Cell Research Center at UCLA.
Embryonic stem cells hold great promise, but they also have raised concerns about whether they will form tumors or create an ear, for example, where physicians wanted them to produce blood.
The placental stem cells have already matured to the point where scientists know what they will get — they will produce red or white blood cells or platelets.
“Nature made them, so they’re perfect,” said Mikkola, who was not involved with the Children’s Hospital study. “That’s why bone marrow transplantation has worked so well. We shouldn’t ignore putting effort on looking at how we can better utilize the stem cells that have already been made.”
Another common way to cure children with blood-related disorders is to transplant them with stem cells from umbilical cord blood. Researchers believe these cells are virtually identical to the ones found in the placenta.
Since 1997, when their sibling donor cord blood transplantation program began, Children’s Hospital has cured more than 100 young people with blood-related disorders.
But there is a drawback to this approach: Umbilical cords provide only a small number of stem cells, making adult transplants difficult.
One of the study’s more promising findings is that the placenta has a several-fold increase in the number of stem cells compared when with cord blood, which could make it easier to transplant adults and larger children.
Leaders at Children’s Hospital were enthused this month to receive a $9.8 million gift from Hayward resident Dolores Jordan to fund research in cellular therapies, including bone marrow and cord blood transplantation.
But more money is needed to further the research on placental stem cells, Lubin said. He and his colleagues expressed frustration that they have not been able to obtain the multimillion-dollar grants that many universities have received from the state agency for embryonic stem cell research, especially since therapies from such research often are many years away.
“No one has been cured by an embryonic stem cell,” Kuypers said. “We are able to cure folks with (blood) stem cells, and you have to wonder, what is important?”
At 19, Kent Klawer had the arthritic left shoulder of an 80-year-old man.
The damage almost forced the Riverside college student to forsake competitive swimming.
Now 23, he’s the beneficiary of a promising surgical procedure called the Graftjacket that saved his shoulder, salvaged his swimming stroke and eased his pain.
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Through tiny incisions into the bone, an orthopedic surgeon covered Klawer’s shoulder socket with transplanted cadaver tissue, its cells removed to prevent rejection. The goal was to allow Klawer’s bone marrow to seep into the graft and eventually regenerate cartilage through his own stem cells.
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That’s exactly what happened, said Klawer’s doctor, Joseph Burns. In fact, he said it was the best outcome he’d ever seen in such a severe case of arthritis. Anecdotal testimonials from Klawer and two biopsies have revealed almost-normal cartilage, Burns said.
“My shoulder is so much better,” said Klawer. He got married, enrolled in a master’s program in counseling at California Baptist University and works as a barista at Starbucks.
“I couldn’t hold my arm up at all,” he said. “We’d go out to eat, the waiter would hand me water, and I’d drop the glass on the table.”
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PIONEERING EFFORT
A swimmer since youth, Klawer’s troubles flared up four years ago when he was an undergraduate at Cal Baptist. “The burning and throbbing in my left shoulder was chronic,” he said.
His pain worsened after traditional arthroscopic surgery in March 2006. That summer he returned home to Santa Clarita and consulted Burns at the Southern California Orthopedic Institute in Van Nuys. A shoulder specialist, he’s considered a pioneer in the use of potentially regenerative material instead of the standard plastic or metal.
After Klawer weighed his options, he agreed that August to the surgery, which his insurance covered.
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Burns vetoed the usual shoulder replacement for Klawer — a metal ball and a thick plastic socket– as a poor option for a young person with advanced arthritis. The inserts work well for people in their 70s and 80s, but eventually wear out, Burns said.
Instead, he turned to the burgeoning field of biologics, using materials that come back to life and is especially widespread in hernia repair, wound healing, foot and ankle surgeries.
Burns noted that surgeons have grafted tissues from cadavers in patients’ shoulders to repair torn rotator cuffs with “very good success” in the past eight years. But using grafts to reconstruct an arthritic shoulder socket is fairly rare, said Burns.
“When you put the graft in, you’re asking the body to grow into the new matrix, make it come alive,” Burns said. He compared the cadaver tissue to an empty building, populated by the body’s own regenerated cells.
The doctor placed a 4.5-by-3.5 centimeter of skin patch from a cadaver’s low back onto Klawer’s shoulder. With the graft’s cells removed, the patient’s body recognizes the tissue as its own rather than as foreign material to cast off. “The patient’s own stem cells inside the shoulder joint from the bone marrow will differentiate into cartilage cells,” Burns said
Klawer began to feel better in three months when the cells started to regenerate. Unlike a shoulder replacement with a plastic insert, the two-hour Graftjacket procedure can be repeated, Burns said.
Klawer needed 1 ½ years to rehabilitate his shoulder.
“The recovery was long and hard,” Klawer said. He still exercises his rotator cuff and is delighted that the shoulder doesn’t hurt when he swims or lifts his left arm.
Burns predicted that Klawer’s graft should last only three or four years. But of the 15 patients with arthritic shoulders on whom he’s performed the surgery, the doctor said that Klawer has shown the most improvement.
“This surgery is the last resort,” Burns said. “I don’t have other good options.”
The Regenerative Medicine Laboratory at the William R. Pritchard Veterinary Medical Teaching Hospital allows for processing, culturing and storing stem cells for horses.The stem-cell lab is one of only four nationwide, and is available to clients and referring veterinarians.
“We are excited to be able to offer this new clinical service to our clients for their horses as a complement to our stem-cell research program,” veterinary medicine school dean Bennie Osburn said. “Stem cell science is leading us into a new era in human and veterinary medicine.”
Regenerative medicine involves creating living, functional tissues to repair or replace tissues or organs that have been damaged by injury, disease or birth defects. Stem cells can be collected and become specific cell types, such as muscle, blood and nerves.
“The stem cell, with its ability to recreate, repair or revitalize damaged organs or tissues, is rapidly changing all of medicine,” said Gregory Ferraro, a veterinary professor and director of UC Davis’ Center for Equine Health. “The application of stem cell science to treating horses is advancing so quickly that with three to five years, the treatments that are currently being provided for orthopedic repair in athletic horses will seem crude in hindsight.”
The UC Davis lab will collect stem cells from the horse’s own blood or bone marrow, and not embryonic stem cells — a controversial issue for human and veterinary medicine.
Horses have benefited from stem-cell therapy in recent years, especially from diseases such as colic and neuromuscular degeneration, burns and other injuries.
“The marvelous thing about stem-cell therapy is that it holds the promise of a cure,” said Sean Owens, a veterinary professor and director of the Regenerative Medicine Laboratory. “We can use pharmacological medicine to alleviate the pain associated with orthopedic injuries in horses, but only with biological medicine such as stem-cell therapy can we actually repair the damage that has already been done.”
The lab, located on the first floor of the UC Davis William R. Pritchard Veterinary Medical Teaching Hospital, will support the clinical area of the veterinary stem cell program. Private veterinarians can harvest stem cells from the lab for their patients and return the cells for processing or storage. Some of the horses undergoing stem-cell therapy treatment could be referred to the teaching hospital.
Stem cell processing and treatment costs will vary. The fee for processing and expansion of a bone marrow sample will be about $1,800. Stem cell injections for most patients will cost about $1,500.
New stem cell studies at the University of Maryland Dental School demonstrate that surgeons could one day routinely use strong, mold-able, and inject-able pastes to regenerate needed bone tissue to repair broken bones, fractures, genetic defects, even combat bone wounds.
The University of California Davis School of Veterinary Medicine has opened a