Rotator cuff tears can be difficult to heal and shoulder surgery can have high complication rates. In addition,rotator cuff repair surgeries are often associated with long recovery and rehab times (think blue pillow immobilizer). Here we present a case of a patient (EZ) who had a 2-3 year history of shoulder pain and after an MRI was told he needed surgery to repair the rotator cuff tear. The patient was a physical therapist, so he knew about shoulder rotator cuff tear non-surgical options and wanted to try and avoid more invasive surgery. Shoulder rotator cuff tear injected under active ultrasound guidance shown here. The patient underwent the Regenexx-PL and Regenexx-SCP injection procedures. These two are different and this will be a good discussion of the differences. Regenexx-PLis platelet lysate-our doctors crack open the platelets to get all of the important growth factors out to be immediately available to the stem cells. This is different than PRP (platelet rich plasma) which has intact platelets and acts as a timed release of growth factors. While PRP (platelet rich plasma) can be very helpful at times, when getting stem cells to grow, our lab experiments have shown that PRP under performs platelet lysate. The Regenexx-SCP procedure uses a lab processed platelet preparation where the smaller blood circulating stem cells are preserved. The result? The images above are from an ultrasound of the shoulder (sagittal cuts with a Sonosite M-Turbo in MSK mode). The pre-treatment pictures are on the left (same pictures stacked on the left-one annotated for problems in the bone and one annotated for problems in the muscle). On the right, again the same image stacked, from two months after the first image. Note the break in the bone and the rotator cuff tear in the pre-treatment images and then the repair of the bone and much less prominent rotator cuff tear in the post-treatment images. The patient now reports no pain in the front of the shoulder with movement overhead. Throwing a softball and playing volleyball is now not painful. Overall improvement is noted at 90%.
Interesting study presented at the Orthopedic Research Society on how shoulder range of motion and stability aren’t restored fully by rotator cuff surgery.Shoulder rotator cuff surgical repair has become the standard for patients with rotator cuff tears seen on MRI and who still have pain and lost function. Most patients believe this surgery is allot like taking your car into the mechanic to replace a worn-out part in that after surgery, the shoulder will perform like new. We’ve seen patients for years who often complain of less function after surgery than they had before surgery, so this study is helpful to see why this happens. The researchers looked at the patient’s shoulder that was operated with rotator cuff surgery vs. the opposite shoulder without the surgery. They used sophisticated high speed x-ray to check on how much the shoulder joint moved. The shoulder movement was analyzed at 3, 12, and 24 months after surgery. They concluded that shoulder strength and joint stability as well as range of motion wasn’t restored. What long-term implications might this have? Shoulder stability is crucial to protect the shoulder joint long-term. Lost range of motion also means that other joints will be have to be used more to compensate. The reason? Shoulder rotator cuff repair is a big surgery that can reconnect severed rotator cuff tendons, but often these tendons can’t be repaired to their pre-tear integrity. In addition, recovery times from shoulder rotator cuff surgery can be long, often in a large pillow immobilizer, which can weaken tissues. Also, fatty atrophy of the rotator cuff may set in (the muscles may get smaller and weaker and get replaced by fat tissue) and this atrophy isn’t helped by shoulder rotator cuff repair. Finally, since any surgery will generally have more secondary side effects effects of tissue damage compared to any injection, we recommend to our patients that if they have a partial rotator cuff tear, a full thickness and non-tracted tear (the ends of the tear are still together), or severe tendinosis (the tendon is aggravated and perhaps frayed), that they try stem cell injection therapy before considering surgery.
Interesting study that shows that 60% of patients who had pieces of their meniscus removed after surgery showed early signs of knee arthritis within years (3.4-8.8 years). Also interesting was that patients who were able to have their knee meniscus repaired fared much better, with only 20% of these patients showing signs of knee arthritis in that time frame. This fits with our prior posts on what happens when pieces of the knee meniscus are surgically removed. The meniscus is a spacer that helps protect knee cartilage. Cutting out pieces of this meniscus spacer only reduces the protection for the knee joint and leads to a more rapid progression of arthritis. What’s interesting about this study is that the patients who had their meniscus repaired fared better, as I blogged on another study that showed that almost all of these knee meniscus repairs really didn’t heal when you went back into the knee to take another look on arthroscopy. My bet is that what we’re seeing here is simply the fact that leaving torn meniscus tissue in a knee is protective (whether or not the repair actually heals). The upshot? Don’t remove meniscus tissue. We can try to repair it surgically, but often that won’t work. However, just leaving it in place and treating these knees non-surgically, in our opinion is a better option than menisectomy.
Patients today have many options to treat a shoulder rotator cuff tear and often explore those options through research on the internet before they decide which treatment (surgical, non-surgical stem cell injection, physical therapy) fits the best. A recent study examined what was the optimal time for surgery of a rotator cuff tear. These patients had a painful tear due to trauma, weakness in the shoulder, and couldn’t fully lift the shoulder to the side and over their head. The study concluded that surgical rotator cuff tear outcome wasn’t compromised (regardless of the rotator cuff tear size) up to four months after injury. Most tears could also wait longer, but patients with massive rotator cuff tears who waited longer than 4 months had the worst outcome. As we advise patients on what type of rotator cuff tears we believe we can treat through injection of their own stem cells under imaging guidance and which types would be better treated via surgical repair (usually the massive rotator cuff tears with retraction of the two ends need surgery), it’s helpful to reassure patients that waiting to make a decision about whether surgery or stem cell injection is right, up top a point, doesn’t seem to impact surgical outcome. While many rotator cuff tears can be treated successfully with the injection of the patient’s own stem cells, if that process doesn’t work, at least in tears that aren’t the massive, retracted type (which we wouldn’t generally treat with stem cells), waiting for surgery to try a non-surgical option, doesn’t seem to negatively impact outcome.
Interesting animal model of tendon healing using stem cell injections to help repair Achilles tendon injuries. The Achilles tendon is the large tendon in the back of the ankle, just above the heel. It’s also known as the “heel cord”. It’s the connection between the strong calf muscles and the heel, allowing forceful push off of the foot while walking and running. An Achilles tendon rupture is the most common injury of a tendon. It occurs more commonly in men and is usually seen in younger athletes or middle aged recreational athletes. In addition, the Quinolone family of antibiotics such as Cipro and Levaquin have recently been shown to be a cause of Achilles tendon ruptures. While this problem is commonly treated with surgery, the most modern randomized trials have showed no benefit to surgery. This is important, as Achilles tendon rupture surgery involves extensive downtime and surgical repairs have a high failure rate. To avoid Achilles tendon surgery, the above study sought to determine if the same type of stem cell mix used in Regenexx-SD might help Achilles tendon tears heal. It compared the injection of a bone marrow stem cell mix to cultured mesenchymal stem cells. What was interesting was that the Regenexx-SD type stem cell injection treatment into the Achilles tendon produced better results than the cultured cells. The authors thought this may have been due to the release of certain healing chemicals from the whole cell mix of the Regenexx-SD type therapy (which contains other stem cell types and other cells involved in tendon healing).
The failure of the cultured stem cells in this animal model may have been due to issues that we’ve observed in other research studies. One thing we’ve noticed is that to get enough cells to create a single treatment, it’s common for researchers to pool the cells of several subjects. In addition, the appearance of the stem cells used in these studies often shows that the cultured cells have been grown for too long a time and are under severe stress (not healthy). This may explain why the cultured cells didn’t work as well as fresh cells from a stem cell concentrate. However, the fact that this study confirms an animal model of tendon healing is consistent with results we’ve observed when we inject the stem cells obtained with the Regenexx-SD and Regenexx-C procedures into tendon tears. In addition, any injection based treatment for tendon tears will be significantly less traumatic and usually have a much shorter recovery time than any open surgical treatment.
A study out this month shows that rotator cuff tears in the shoulder are common in elderly patients with diabetes. This makes sense, as based on our stem cell culture experience with Regenexx-C, diabetic patients were less likely to have stem cells capable of growing to high numbers in culture. This study showed more shoulder joint effusions (swelling) in diabetics as well as swollen tendons (such as biceps). In addition, diabetics had more tears in the supraspinatus (one of the muscles of the shoulder rotator cuff). The authors discussed that in diabetics, routine shoulder imaging with ultrasound may be a good way to prevent major tears from occurring. This also would be a great application for stem cell therapies like Regenexx-SD or Regenexx-SCP, where injections of these cells could be performed using ultrasound guidance to deliver cells to the exact weak areas and minor tears, hopefully to prevent a full thickness rotator cuff tear from developing (one that might only be successfully treated with higher risk surgery). This approach may make financial sense as well, since shoulder rotator cuff surgery is less successful in diabetics when compared to patients without diabetes. If you add this shoulder treatment approach to the success we’ve already seen in helping patients with rotator cuff tears avoid surgery by injecting their own stem cells, this may be a great way to deploy stem cell therapies for shoulder problems in the future.
The Centeno-Schultz Clinic and the Regenexx stem cell procedures for orthopedic injuries were featured in the January issue of Life Extension magazine. The link isn’t yet available on-line (the Jan issue is on newstands now), but here is the copy of the article which was sent to me by the author, Julius Goeb, M.D.:
Joe is a 58 year-old man in a painful Catch-22 situation. He’s had chronic pain in both knees for 12 years, attributed by his doctors to osteoarthritis resulting from his time in the military doing long marches with heavy weights. The pain in his right knee is so severe that it often limits how far he can walk, and tennis, his go-to sport for as long as he can remember, has been out of the question for a decade. He has undergone 3 arthroscopic surgeries, which provided only transient relief.
Like many middle-aged people, Joe suffers from a chronic age-related condition. He would seem to be the perfect candidate for total knee replacement surgery. But, paradoxically, his doctors advise him that he’s too young! Knee replacements don’t last forever, so orthopedists typically like to defer the first surgery for as long as possible. So Joe takes high doses of pain relievers and gets the occasional injection of an anti-inflammatory steroid while he grows older in significant pain.
Until recently, Joe’s story was typical for middle-aged patients, but the situation is rapidly improving, thanks to breakthroughs in tissue engineering and the modern science of autologous stem cell transplantation. This article is about that procedure and how it can bring relief to men and women in Joe’s situation. You will understand how the procedure uses patients’ own adult stem cells to re-grow cartilage, tendon, ligament, and even bone. You will discern the difference between this and the ethically troubling field of embryonic stem cell research. You will read impressive results of laboratory and human studies, and you’ll see a summary of the largest clinical experience to date, from one leading clinic in Colorado. You’ll also read about shocking and illogical steps by the FDA that have temporarily halted the most productive form of these procedures in a naked power play by big pharmaceutical companies. Finally, you’ll learn of the courageous and defiant steps taken by the clinic’s founders to confront the agency and hold it accountable. But let’s start with the basics — what happens in common joint disorders, and how autologous stem cell transplantation holds promise for repairing them in astonishing ways.
Busted Joints, Broken Dreams
Joe’s problem, osteoarthritis (OA), is a common and debilitating one in the USA and around the world. Joints affected by OA undergo gradual degradation of their cartilage, the natural slippery, lubricated surfaces that allow smooth movement and weight-bearing.1 As the cartilage deteriorates, friction increases, leading to pain and ultimately actual destruction of the joint.2 But cartilage is poorly supplied by blood, making it slow to heal, and damaged cartilage will not regenerate itself under normal circumstances.3, 4 And since OA is common in previously physically-active people, it can significantly impair quality of life in those who suffer from it, particularly as they age.5-7
Many modern surgical repair procedures are actually aimed at disrupting cartilage deeply enough to trigger a repair response from the bone underlying the cartilage, but the result is often incomplete and inadequate.7, 8 Over the past several decades, surgeons have developed techniques for removing small “plugs” of healthy cartilage from uninvolved areas of joints and transplanting them into the damaged areas, sometimes culturing the cells first to increase their numbers.2, 4 While these techniques have shown some promise, they have the disadvantages of damaging otherwise intact cartilage, and they still don’t restore joint function adequately.3, 7
In many patients, therefore, the only solution is to wait until the disease becomes severe enough, or the patient old enough, to warrant full-scale artificial knee replacement. And total knee replacement is major surgery, with patients typically advised to count on up to 6 weeks of limited activity, and 6-12 months of gradual rehabilitation to return to normal function.9 That alone explains orthopedists’ keen interest in discovering faster and simpler solutions. The answer, as it happens, lies within.
Autologous Mesenchymal Stem Cell Transplantation — A Personal Solution
Most people have heard of stem cells — the powerful precursor cells that can differentiate, or mature, into virtually every type of tissue in the body. But early work with stem cells involved “harvesting” them from human embryos, which raises a host of ethical issues. And embryonic stem cells, precisely because they are so versatile, carry the risk of transforming into tumor cells as well.10
More recently, attention has focused on a small number of alternatives to embryonic stem cell therapies. When it comes to bone and joint regeneration, the most promising approach seems to be the use of so-called mesenchymal stem cells (MSCs) taken directly from the patient’s own body.11 Unlike embryonic stem cells, these cells have already differentiated to some extent, “committing” themselves to develop into tissues such as bone, muscle, tendon, ligament, and cartilage.11, 12 And conveniently, mesenchymal stem cells can be found in significant numbers in the bone marrow.12 Under the proper conditions, MSCs can be induced to differentiate into each of their potential specific tissue types, making them the ideal “seeds” for implanting into damaged joints and bones.
One advantage of using MSCs from a patient’s own body (autologous) is obvious: there is zero risk of transplant rejection. Perhaps equally important, there’s now evidence that transplanted MSC’s actually have powerful anti-inflammatory, immune-modulating powers within the joint.2, 13 That means they may actually out-perform more traditional transplants, which run the risk of destruction by inflammation. And most significantly, these autologous mesenchymal stem cell transplants work in astonishing ways to repair cartilage, bone, and connective tissue.
Animal research from the mid-1990’s onward has provided ample proof of this amazing concept. The first researchers used cartilage “progenitor” cells from just beneath the cartilage layer, growing them in culture and then injecting them into damaged knee joints.14 The result was complete repair of the damaged cartilage and reformation of injured bone beneath it. That study was followed by a host of others using true mesenchymal stem cells from bone marrow, with even more dramatic results showing functional cartilage that appeared nearly identical to normal healthy joint tissue.15-19 Advanced imaging studies have now demonstrated that MSCs migrate into the damaged structures following injection, where they take up residence and contribute both directly and indirectly to the repair process.20
But can autologous MSC transplants help human patients with arthritis and other bone and joint problems such as lumbar disc conditions and unhealed bone fractures? The answer is a qualified “yes,” qualified not because of problems with the procedure, but rather because of an absurd bureaucratic move by the FDA that may vastly exceed its authority. Let’s start with the good news, and examine the groundbreaking work of Dr. Christopher Centeno and his colleagues at Regenerative Sciences, Inc, in Westminster, CO.
From the Lab to the Clinic: Introducing Dr. Christopher Centeno
Dr. Centeno is an international expert and specialist in regenerative medicine. Soon after the turn of the present century, Centeno became interested in applying what was known about the powers of stem cells to solving problems in orthopedics. Because orthopedics is the practice of medicine devoted to the health of bone, joint, muscle, and connective tissue, mesenchymal stem cells were the obvious choice for his research.
Centeno was aware of the rapidly-growing success of MSCs in animal studies, and he was also painfully cognizant of the failure of traditional treatment of osteoarthritis and similar diseases.21 He knew that human bone marrow contained an adequate supply of MSCs that could readily be “harvested” from a patient’s own hip bone. And crucially, he suspected that one could use the patient’s own tissue growth factors, obtained from a “puree” of their own platelets, to trigger those MSCs to replicate and prepare to grow up into functional cartilage and bone that might repair damaged joints.21 (See SIDEBAR) Once the cells had been “amplified” in culture with activated platelets, Centeno reasoned, they could be injected into a diseased joint. Animal studies had demonstrated that such cells would proceed to further differentiate into the proper cell types based on local tissue factors produced by the surrounding healthy structures.
In two seminal 2008 papers, Centeno presented the results of his first human patient, a man much like Joe who’d had a long history of chronic knee pain unresponsive to surgery.11, 21 Centeno’s patient underwent successful harvest, expansion (through platelet-derived tissue factors), and transplant of his own MSCs into his damaged knee joint. The results were spectacular — by one month after the injection the patient’s cartilage surface had expanded by more than 20%, a gain that was maintained at a 3-month visit. And the meniscus (the lower cartilage that actually bears weight) was nearly 29% larger in volume at 3 months, indicating vigorous growth and remodeling of previously damaged tissue. More importantly, the patient’s pain level dropped from 4 out of 10 to just 0.4, and his range of motion, previously limited, became nearly normal.
Since that time, Dr. Centano and his colleagues have completed hundreds of autologous MSC transplants in patients with both knee and hip joint disease. Their most recent outcome data shows that for knee pain, more than 60% of their patients report a greater than 50% reduction in pain, and fully 40% report more than a 75% reduction.25 Hip pain patients report greater than 50% relief in about 42% of cases, with more than 75% relief in about 23%. Those numbers are impressive on their own, and much more so in the context of the simplicity and ease of doing the transplant procedures compared with major surgery.
Centeno is rigorous about following up his patients to determine their short- and long-term outcomes, both functional and safety-related. He has recently submitted a paper reporting on 339 patients, with focus those with knee osteoarthritis.26 Almost all of those patients had been told by their physicians that they would need a total knee replacement. But over the entire observation period, just 4.1% of Centeno’s patients wound up actually requiring surgery — the rest achieved adequate relief from the stem cell procedures. Centeno also compared his patients’ procedure-related complication rates with those of patients undergoing traditional knee replacement surgery. Among his patients, no serious complications were attributed to the procedure. But based on published data for knee replacement surgery, Centeno calculates that in a similar sized group of surgical patients,27 29-37 would have had serious surgical complications, including 1-2 deaths, and as many as 16 hospital re-admissions for serious infections.26
Of course, safety is everyone’s concern when using stem cells of any kind, because of the known risk of tumors with embryonic stem cells. Dr. Centeno and his group have recently published the largest safety study to date in patients undergoing autologous bone-marrow-derived stem cell transplants for orthopedic conditions.28 They followed 227 patients for up to 2 years following the procedure, including a large group in whom high-definition MRI scans were available. They found no cancer-like complications at any stem cell transplant site.
Those findings are consistent with those of other pioneers in the field. Japanese researchers reported finding neither tumors nor infections after 45 transplants with follow up periods of up to 11 years (mean 75 months).19 And orthopedic surgeons in Singapore reported that the stem cell procedure produced outcomes equivalent to cartilage repair using chondrocyte implantation (a surgical procedure), with fewer complications and at lower cost.29 In fact, transplant patients had superior physical functioning compared with the surgically-treated group.
By mid 2010, global expert Shigeyuki Wakitani of Japan’s Osaka City University was able to write, “Bone marrow-derived mesenchymal stem cells (BMSCs) are the most widely used worldwide to repair not only mesenchymal tissues (bone, cartilage) but also many other kinds of tissues.19 It would seem, then, that Dr. Centano and others in his field would soon be expanding their work to benefit thousands more patients here in the United States. Unfortunately, here’s where the story darkens (albeit, one hopes, temporarily).
Your Body, Your Cells? Not Necessarily, Says FDA
In an astonishing and perplexing move, the federal Food and Drug Administration (FDA) is seeking to enjoin the clinic physicians from practicing medicine using the patient’s own stem cells. The FDA action equates these cells, taken from the patient’s own body, with drugs manufactured in large factories producing millions of doses, and the agency seeks to regulate those cells just as it would drugs. That tortured logic, if applied across the board, could cost patients millions.
“If physician practices and hospitals must now use the same standards as drug manufacturers, expect medical care costs to skyrocket without any measurable impact on safety”, stated Centeno, who is taking the matter to court.
“The FDA finally will answer our questions, in court, about their claims and jurisdiction as opposed to doing everything in their power to avoid the issue that we are not a drug manufacturer, but simply a medical practice,” says Centano. He continues, “This is an important case for everyone that suffers from any type of illness, not just patients with orthopedic problems. It will decide, once and for all, if the government has the right to restrict a patient and their doctor from using a person’s own stem cells to treat disease. Regenerative Sciences believes that stem cells are body parts and not the property of the government or big pharma.”
In fact, there’s precedent (as well as plain logic) supporting Regenerative’s position. “What we’re doing in our medical practice is no different, in principle, than a fertility clinic that uses the in-vitro fertilization technique,” says John Schultz, M.D., Centano’s colleague and co-founder of the clinic. “The only difference is that we’re using stem cells and fertility clinics use fertilized eggs.”
For the time being, Regenerative has halted the part of its work that involves culturing a person’s cells to enrich the population of MSCs prior to transplantation, which is the portion of the procedure the FDA believes it can regulate. Meanwhile, fortunately, the team has developed a same-day procedure that involves no cell culture. MSCs are harvested from the hip bone marrow space, purified, and directly injected into the damaged joint. This procedure can deliver fewer activated MSCs to the site, but it is free of the bureaucratic muddles of the more intensive treatment.
Centeno remains optimistic, confident that he and his colleagues will prevail. He cites David Audley, director of the International Cellular Medicine Society, who stated that “The Centeno-Schultz Clinic meets our strict criteria for the safe therapeutic use of adult autologous stem cells. There is more medical and scientific evidence supporting this type of medical therapy for orthopedic conditions, for example, than there is for many approved drugs that the FDA allows to be used in off-label or unconventional applications.”
Sufferers of osteoarthritis and many other bone and joint diseases have good reason to hope for relief in the near future, based on the groundbreaking work of Dr. Christopher Centeno and his colleagues, and others like them around the world. These visionary clinical practitioners have pioneered the use of safe and simple autologous mesenchymal stem cell transplants to repair and replace damaged cartilage and other bone and joint structures. Unlike embryonic stem cells, autologous MSC transplants use patients’ own cells that are already committed to developing into skeletal tissues, eliminating both the risk of transplant rejection and of tumors. And the procedure is non-surgical, dramatically lowering both cost and risk, and similarly reducing pain and recovery time. Unfortunately, the FDA has thrown a temporary wrench into the works, claiming that a patient’s own cells somehow become drugs when used in these procedures. But because of the courage and steadfastness of the leading players in the field, the agency will now have to define its position in court, or abandon it and allow progressive clinicians to practice medicine using safe and internationally-established techniques.
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