A team of doctors in colorado have pioneered a procedure that avoids joint replacements, but the FdA quickly stepped in, attempting to outlaw it.
Behind an unassuming doorway in an industrial park housing a Walmart and cookie-cutter office blocks lies a small clinic with a decidedly immodest goal. Its stated purpose is nothing less than to transform all of orthopaedic medicine simply by tapping into the healing force within the patient’s own body. Owner and medical director of the Centeno-Schultz Clinic, Dr Chris Centeno, a 51-year-old pain management specialist, is quietly transforming orthopaedic medicine after pioneering a technique that uses the patient’s own stem cells to restore damaged tissue-cartilage, bone, ligaments and tendons-largely ending the need for surgery. A typical patient of his is Joe Maroon, whose knee was giving way to osteoarthritis and so was being faced with
an impossible choice. After years of running, biking and swimming, Maroon’s cartilage had significantly deteriorated, causing constant pain. Doctors told the 63-year-old triathlete that he needed knee replacement surgery, but as a doctor himself, a neurosurgeon at the University of Pittsburgh, he was well aware of what that might well entail. Had he been just a few years younger,
his doctor might not have even presented that option; artificial hips or knees wear out after about a decade and then need to be replaced again, so doctors like their patients to defer that first operation for as long as possible.
The only alternative was a lifetime of steroid injections and the overwhelming likelihood of having to end his competitive sporting activities. During his years of waiting, Maroon chanced upon
the Centeno-Schultz Clinic’s orthopaedic alternative RegenexxTM, which relies on using a patient’s own stem cells to heal damaged joints. Maroon was impressed enough to travel to the tiny clinic in Broomfield, a suburb outside of Denver, Colorado, to consult with the specialist who’d pioneered what he was touting as an alternative to surgery. After some of Joe’s stem cells were extracted from his bone marrow, they were cultured and so multiplied in the laboratory over several weeks before being reinjected into his damaged knee. The result was such a reduction of pain that Maroon, by that time aged 68, was able to compete in the Ironman Hawai’i triathlon six months later.
The doctor behind Joe’s remarkable recovery is pioneering a new kind of orthopaedics, one that avoids surgery and relies on the patient’s own body to heal. Centeno was profoundly dissatisfied with the state of orthopaedic medicine, and its reliance on steroids and surgery. Most joint issues are caused by deterioration of cartilage-which cushions the movement of bones, especially in the hips and knees-usually due to inflammation. As cartilage is poorly supplied with blood, it ordinarily doesn’t regenerate. Medicine makes tacit recognition of this fact with the few alternatives to joint replacement it offers. Surgery to repair cartilage either attempts to ‘injure’ it to prompt the bone beneath it to initiate a repair response, although such procedures often don’t work very well, 1 or chunks of healthy cartilage are implanted into areas of damage as a form of tissue engineering. 2 Both have a spotty record of success, mostly because the transplants are often
destroyed by the body’s own natural inflammatory response. After the turn of the millennium, Centeno became interested in animal research on stem cells, 3 and wondered whether it might apply to people too. The research was showing that when damaged joints were injected with the animal’s own stem cells, the cells-as if responding to some hidden blueprint-as well as the
tissue surrounding them would differentiate into the appropriate tissues required to heal the damage. Even more encouraging, the tissue continued to do its repair job over time.
Centeno wanted to test whether the ready supply in the bone marrow of most patients of malleable mesenchymal stem cells (MSCs), which are already likely to turn into bone, cartilage and connective tissue cells, could be used to rebuild damaged joints. Centeno’s ‘ah-ha’ moment came when he realized that adding to the brew a solution of the patient’s own blood platelets would ‘supercharge’ the MSCs to both replicate and also to differentiate into more cartilage and bone to repair the joint. Centeno partnered with Dr John Schultz, an orthopaedic specialist and anaesthesiologist, and the Centeno-Schultz Clinic opened its doors in Broomfield. Early on, Centeno had also decided to substantiate the clinic’s work by carrying out painstaking research
and follow-up on all their patients and publishing the findings, ultimately spending $500,000 of his own funds on mainly research programmes. So far, Centeno has carried out more research on stem-cell orthopaedic repair than has any other research centre.
In 2008, he published the results of the first patient to undergo his procedure. His guinea pig was a man who’d suffered for years from knee pain that had not improved with surgery.
Centeno harvested MSCs from the patient’s hip bone (see box, page 26), and multiplied and ‘boosted’ them by culturing the cells with tissue factors from the patient’s blood platelets. After a few days, he injected this brew into the patient’s knee. The results were unequivocal. Just a month after the procedure, the patient’s knee-cartilage surface area had expanded by more than 20 per cent, and the joint meniscus-the cushiony cartilaginous pad that bears the brunt of the thigh bone’s weight-was also 29 per cent larger after six months. 4 The patient’s previously limited range of motion was now nearly normal and his pain, formerly assessed as 4 out of a possible 10, had plummeted to 0.4. Impressive results In the intervening six years, Centeno and his colleagues (including doctors he has trained around the world) have performed some 10,000 procedures on all manner of orthopaedic and soft-tissue injuries, hundreds of them involving patients with diseased knee and hip joints. The results are impressive-even more so because his patients continue to improve over time, month after month, year after year. Recently, his registry
data showed that, of 221 overweight (body mass index scores of more than 25 kg/m2) and older patients with knee arthritis, 80 per cent recorded more than 25 per cent improvement after the operation, with an average of nearly 60 per cent improvement after two years. And of 999 middle-aged people who were only slightly overweight, the figures showed that 90 per cent reported
a more than 50 per cent improvement , with more than 70 per cent average improvement after four years.
Although the results for hip pain are not as spectacular, more than 60 per cent of such patients still reported more than 25 per cent pain relief, with an average improvement of 42 per cent in patients under 55 (22 per cent if older than 55). Puzzling over why hip patients don’t do as well as knee patients, the RegenexxTM team studied their post- treatment registry and discovered that a patient’s total range of hip motion was connected to outcome success; the poorer the range of motion, the poorer the outcome of the standard treatment (where injections are the patient’s own stem cells are just injected back in). Nevertheless, both hip and knee stem-cell patients fare well when compared with joint-replacement patients. According to an independent comparison
made by American orthopaedic surgeon Dr Mitch Sheinkof, patients getting hip replacements showed a greater improvement in the Harris hip test (which measures pain and movement ability), but RegenexxTM patients enjoyed better range of motion and a better overall risk/benefit equation, as the stem cell procedure is far less invasive and carries far less risk. Some 73 per cent of the hip RegenexxTM patients were able to return to sporting activities. Knee patients in particular show greater overall functional improvement (see page 31). n 2011, Centeno and his team published a safety and complic
ations report of 339 patients, most of whom had arthritis of the knee and all of whom had been told they needed knee replacements. After receiving the stem-cell RegenexxTM treatment, only 4.1 per cent of these patients went on to get an artificial knee, while the rest did well enough with the RegenexxTM treatment to avoid surgery. 5 Besides diseased joints, Centeno’s clinic handles all kinds of soft tissue and spinal injuries. Spending an afternoon listening to stories in the busy clinic’s waiting room is instructive. In a typical case, an elderly
woman so damaged with arthritis she could barely walk says she’s become a mountain climber since having the procedure; another woman, whose knee anterior cruciate ligament was damaged 20 years ago playing basketball, has seen it repaired with the stem-cell procedure. Patients with rotator-cuff injuries, tendonitis, spinal injuries, deteriorating discs-all are open to repair without the often catastrophic effects of surgery. “With this type of medicine, we can move from managing pain to actually curing the injured tissue,” says Centeno. “Imagine-knees, hips, backs all fixed. No more pain. No more surgery. No more meds. All you need are your own stem cells. Doctors would start actually curing disease instead of prescribing drugs to manage disease, and that’s a groundbreaking paradigm shift.” Not surprisingly, the US Food and Drug Administration (FDA) doesn’t like this paradigm shift one little bit. Autologous (donor and recipient are the
same person) stem-cell therapy not only threatens to revolutionize orthopaedic medicine as we know it, but it also threatens to wipe away some of the lb30 billion pain-management drug business and to ultimately rock the foundations of FDA control of the entire drugs marketplace.
The FDA, now largely funded by the pharmaceutical industry, has visited the Colorado clinic multiple times, sifting through Centeno’s laboratory “as if it were a mass drug manufacturing factory”,
he says-and unlike most doctors, he decided not to take this harassment lying down. In August 2010, the Center for Biologics Evaluation and Research, a division of the FDA, filed an injunction
against Centeno, ordering his clinic to stop culturing patients’ stem cells. In response, Centeno filed for multiple temporary restraining orders simultaneously in Denver and in Washington, DC. The FDA then issued an injunction against the clinic, whereupon Centeno abandoned the restraining orders and promptly countersued the FDA for interfering with his trade. The FDA maintains that extracting, manipulatingand culturing a person’s stem cells constitutes a ‘cultured drug product’ not unlike culturing an antibiotic. In 2012, in an attempt to control this new medical technique, the FDA ruled that your own stem cells should now be considered a ‘drug’ subject to the agency’s control. The FDA’s ruling was held up in a court case, even though Centeno argued that “stem cells are body parts and not the property of the government or Big Pharma”. “What we’re doing in our medical practice is no different, in principle, than a fertility clinic that uses in-
vitro fertilization,” says Schultz. At the time, this meant that Centeno’s clinic could only treat those parts of the body that receive enough blood flow to benefit from an ordinary stem-cell.
M is for mesenchymal
Stem cells are nothing less than shape-shifters-precursor cells that go on to differentiate into whatever kind of cell tissue is required. Stem cells have most controversially been harvested from human embryos and adipose (fat) tissue, but those with the best record of success and safety for treating joint problems are the so-called mesenchymal stem cells (MSCs), found in large numbers in bone marrow tissue. Although other clinics use stem cells from adipose tissue in joints, Centeno believes that MSCs are superior because these cells are already partially committed to
becoming bone, muscle, ligament or tendon, and are easily harvested from bone marrow and reproduce rapidly, making them ideal candidates for repairing those very structures. 1 According to Centeno, under certain conditions, MSCs can be prompted to differentiate into the specific sort of tissue needed; when implanted into affected joints, these cells work to repair cartilage and bone, and even the connective tissues in between. Indeed, there’s even evidence they can protect against inflammation-related tissue damage and have the ability to modulate autoimmune responses too. 2
RefeRences
1 Curr Opin Biotechnol, 2004; 15: 406-10; Pain Physician,
2008; 11: 343-53
2 Arthritis Res Ther, 2008; 10: 223; 2009; 11: 211
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