We see more and more patients calling us these days who finally have a few local options for bone marrow stem cell therapy for their orthopedic problems. As the original clinic in the U.S. doing this work, we applaud this expansion of options for patients. However, we also continue to hear from patients that physicians are performing these procedures without any type of imaging guidance. Imaging guidance means that the doctor can see where the needle is going. This is doubly important in the procedure used to harvest the stem cells: a bone marrow aspiration. While many physicians who are just starting to use bone marrow stem cells to treat things like knee, shoulder, hip, ankle, and hand/foot problems may believe they can take an accurate bone marrow aspirate without knowing where the needle is located, a simple anatomy review will show why this isn’t the case. Above you can see a slice through the PSIS area of the back of the pelvis (near the dimples of Venus). This is the most common bone marrow aspiration site to obtain stem cells. Note that the red arrow points to a section of the bone that’s paper thin and that the green arrow points to an area where it’s very thick. These areas are very close together, such that a needle that happens to get into the thin area will get no bone marrow (which is located inside the bone), but simply go through and through the bone, leading to a slow draw of blood that contains few of the stem cells sought. However, a needle that is guided to the correct thick area can easily tap into the bone marrow space and collect stem cells. How did we learn this? 5 years ago as we started to culture cells, we learned it the hard way. A sample from the thin area produced no measurable cells in culture, while a needle into the thick area produced good cultured stem cells. The upshot? When taking bone marrow, a “blind” procedure (without fluoroscopic or ultrasound guidance) is likely to sometimes collect no stem cells. In addition, since the bedside centrifuges used by many physicians have no way to measure what’s obtained (unlike a full level 3 lab), the doctor never knows he’s just taken a bad sample that won’t help the patient, as a bad sample looks just like a good sample!
You know the saying, “there is no free lunch”? Well, several recent studies have rained on the parade of the embryonic stem cells and IPS crowd. A recent piece in the LA times quoting a paper published this week was more percipitation. The problem is that these cell lines have inherent genetic problems. This means that the cells don’t have normal genes, which raises the specter of unintended consequences when these cells are used for therapy (the biggest being cancer). The reason should be clear by now. Embryonic stem cells (or likely even adult stem cells) that are “immortalized” (artificially tricked into growing forever so that they can be mass produced like an antibiotic) pick up these genetic abnormalities because these cells were never designed by nature to have the DNA repair mechanisms that would allow them to be grown for these great lengths of time. For example, everyday, dividing cells in your body pick up back pieces of DNA or errors. We have enzymes that help repair the damage and a secondary line of defense (called the immune system) to yank the malfunctioning cells out of circulation. However, embryonic (or even adult stem cells) were never designed with the mechanisms to be grown for thousands of generations. An embryo is conceived, it grows bigger, and eventually a baby with adult stem cells is born. Nowhere in there was the embryo designed to grow embryonic stem cells for years for the purposes of satisfying a human need for mass produced biologic tissue. How about IPS cells? For those of you who are unaware, IPS means induced pluripotency, which is a fancy way of saying that a normal adult cell is turned into a cell that resembles an embryonic stem cell. Now since this doesn’t even happen in nature, the process of tricking a cell to revert back to the properties of a stem cell is bound to have issues (which many IPS researchers have been very honest about from the start). Again, since normal adult cells aren’t built to divide forever like IPS cells, the same discussion above applies. If you’re seeing a trend here, you’re not the only one. In both instances, it’s our need to create cells that can be mass manufactured to satisfy a business model that creates the problem. How about adult stem cells like those used in the Regenexx procedure family? Adult stem cells are built to do what we’re asking them to do. They help repair tissue and then either differentiate into the bricks and mortar of the repair or they orchestrate the construction job and then disappear from the scene. Growing adult stem cells for short periods (like in the Regenexx-C procedure), still keeps the cells within the parameters of what happens in the body. Studies have shown no significant genetic abnormalities when adult stem cells are grown for short periods and more interestingly, when they are grown very long periods (months and months) and do pick up genetic abnormalities, they don’t form cancers, they just don’t work anymore. Our complications tracking data has also shown that using these short-term cultured stem cells in people poses less risks than the surgical procedures they help many patients avoid. This is consistent with the findings of others showing robust safety for cultured adult stem cells from bone marrow.
In summary, you can’t teach an old dog new tricks (I think that’s my third really bad turn of phrase). Trying to mass produce cells isn’t a good idea with our current state of knowledge. A better idea is using the patient’s own adult stem cells, which is the “customized” medicine long sought by physicians. While the business model may not be as good, it’s sure a heck of a lot safer for the patient.
Many times in the United States, high grade ankle ligament tears (grade 3) are surgically repaired. This is despite their being a paucity of evidence that this is the best course of action for high grade ankle ligament sprains. A recent study of randomly assigned grade 3 ankle ligament sprain patients looked at this issue. In the study, there was a surgically treated group and one that used an ankle brace. Both groups of grade 3 ankle sprain patients got back to activity about the same. The advantage of the surgical group was less recurrance of re-injury of the ankle ligaments. The big disadvantage for the surgically treated ankles, more ankle arthritis. Why would surgery of the ankle ligaments cause more arthritis down the road? The answer may be in another study showing that lateral ankle ligament surgery and repair actually lead to abnormal motion of the foot and ankle. When a joint moves abnormally, we frequently see more arthritis, as parts of the joint can become worn out more quickly. For the ankle, this may be caused by the fact that restoring normal ankle ligament tension and position may be very difficult to nearly impossible. In our clinic, we often see patients after ankle ligament surgeries that are left with ligaments that are too tight. These artificially tightened ligaments can cause abnormal motion in the ankle. As a result, we frequently council our patients to avoid ankle ligament reconstruction surgery. Non-surgical methods of repair (like injecting the patient’s own stem cells into the ankle ligament tear), in our experience, are often more effective and should be attempted before considering an ankle ligament surgery. In essence, based on the published research, ankle ligament surgery should be a last ditch effort to make the ankle more functional and not a first line treatment for ankle ligament injury or severe sprain.
A recent study looked at whether surgically repairing the outside ankle ligaments (lateral) actually restored the normal way the foot and ankle should move. The outside ankle ligaments are important for stabilizing the ankle (keeping everything properly aligned) as we walk and run. As a result, the study tested the whole reason for performing surgery, restoring normal movements. However, if the surgery failed to restore those normal motions, then the surgery may actually cause problems down the road with certain parts of the ankle wearing out faster due to the abnormal motions. The verdict? No type of lateral ankle ligament repair restored normal motion to the foot and ankle. This is a huge problem for patients considering ankle ligament surgery and repair, because the whole concept behind the invasive surgery and extended recovery time is that the surgery will restore normal motion to the unstable ankle and allow the patent’s ankle to be used like it was before the injury. As a result of these and other research findings, we frequently council patients to consider non-surgical options for an ankle ligament tear. This is especially true when the ankle has intact ligament fibers (a partial tear or a full thickness tear without retraction). Non-surgical treatment can often be performed through a needle without the need for surgery. We feel this approach is better, as any approach that involves artificially suturing or replacing parts of the ankle ligaments (as the above study reveals), doesn’t restore the normal motion. We’ve seen patients report success when the patent’s own stem cells are injected into the ankle ligament tear using either x-ray or ultrasound guidance to ensure the stem cells get to the right spot in the ankle ligament tear. In summary, the vast majority of patients we speak to believe that the research supports that surgery is the best option for the ankle ligament injury, however, we believe the research support for this invasive approach is still lacking.
Bone spurs come in two flavors, functional and non-functional. Despite this, many patients consider a “bone spur” a bad thing. Patients often believe that bone is like inanimate cement. However, it’s really more like living hard plastic. It responds to new forces placed on it. Bone spurs occur when the joint is unstable or a part of the joint needs “shoring up”. Two interesting examples are in the knee. When a patella (knee cap) is pulled too much to one side, the joint responds by adding new bone (essentially extending the joint out further in the that direction). We call this new area a “bone spur” but it’s really just a new part of the joint that’s been created through local stem cells. Another example is when the post-surgical meniscus starts spitting outside the joint and bone spurs are created out in that direction to take advantage of the new position of the meniscus. In both of these examples, these bone spurs are functional, because they allow the joint to work better.
Non-functional bone spurs can begin life as functional spurs, but at some point too much bone is laid down and this dramatically reduces the range of motion of a joint. Literally the new bone gets in the way of normal joint motion. These can be removed surgically, but did you know they can be removed through a needle? This new technique is called barbotage. The area is numbed and then a needle is placed under ultrasound guidance to break up the bone spur. The spur is then naturally reabsorbed by the body and the joint can now move freely. This is a great example of how stem cell therapy can be combined with advanced image guided needle techniques to help restore normal joint function. Here’s what a patient, about two months out from this treatment had to say:
Overall My ankle feels much better. Range of motion – 20% better – Overall pain relief – 40% better. Now I can stand for long periods of time (e.g. 2 hours) , whereas before I could only manage 30 mins max. I can also manage cycling (no pain) and some elliptical trainer (running machine work –approx 15 mins). I’m hoping for further improvements in the range of motion as the strength is (slowly) restored. Overall I’m very pleased with progress to date.
So, in this case, it appears that treatment of a non-functional bone spur can be performed without surgery and that this can improve range of motion and function. Since this was non-surgical, recovery time is also shorter.
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.
1. Csaki C, Schneider PR, Shakibaei M. Mesenchymal stem cells as a potential pool for cartilage tissue engineering. Ann Anat. 2008 Nov 20;190(5):395-412.
2. Ringe J, Sittinger M. Tissue engineering in the rheumatic diseases. Arthritis Res Ther. 2009;11(1):211.
3. Hwang NS, Elisseeff J. Application of stem cells for articular cartilage regeneration. J Knee Surg. 2009 Jan;22(1):60-71.
4. Bedi A, Feeley BT, Williams RJ, 3rd. Management of articular cartilage defects of the knee. J Bone Joint Surg Am. 2010 Apr;92(4):994-1009.
5. Caspersen CJ, Kriska AM, Dearwater SR. Physical activity epidemiology as applied to elderly populations. Baillieres Clin Rheumatol. 1994 Feb;8(1):7-27.
6. A WD, Toksvig-Larsen S, Roos EM. A 2-year prospective study of patient-relevant outcomes in patients operated on for knee osteoarthritis with tibial osteotomy. BMC Musculoskelet Disord. 2005;6:18.
7. Mobasheri A, Csaki C, Clutterbuck AL, Rahmanzadeh M, Shakibaei M. Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy. Histol Histopathol. 2009 Mar;24(3):347-66.
8. Redman SN, Oldfield SF, Archer CW. Current strategies for articular cartilage repair. Eur Cell Mater. 2005;9:23-32; discussion 23-32.
9. Dalury DF, Tucker KK, Kelley TC. When Can I Drive?: Brake Response Times After Contemporary Total Knee Arthroplasty. Clin Orthop Relat Res. 2010 Aug 11.
10. Bongso A, Fong CY, Gauthaman K. Taking stem cells to the clinic: Major challenges. J Cell Biochem. 2008 Dec 15;105(6):1352-60.
11. Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008 May-Jun;11(3):343-53.
12. Jorgensen C, Gordeladze J, Noel D. Tissue engineering through autologous mesenchymal stem cells. Curr Opin Biotechnol. 2004 Oct;15(5):406-10.
13. Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther. 2008;10(5):223.
14. Wakitani S, Goto T, Pineda SJ, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994 Apr;76(4):579-92.
15. Im GI, Kim DY, Shin JH, Hyun CW, Cho WH. Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J Bone Joint Surg Br. 2001 Mar;83(2):289-94.
16. Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003 Dec;48(12):3464-74.
17. Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T. Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation. J Histochem Cytochem. 2005 Feb;53(2):207-16.
18. Chang F, Ishii T, Yanai T, et al. Repair of large full-thickness articular cartilage defects by transplantation of autologous uncultured bone-marrow-derived mononuclear cells. J Orthop Res. 2008 Jan;26(1):18-26.
19. Wakitani S, Okabe T, Horibe S, et al. Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med. 2010 Jul 5.
20. Jing XH, Yang L, Duan XJ, et al. In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Joint Bone Spine. 2008 Jul;75(4):432-8.
21. Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells. Med Hypotheses. 2008 Dec;71(6):900-8.
22. Schallmoser K, Rohde E, Bartmann C, Obenauf AC, Reinisch A, Strunk D. Platelet-derived growth factors for GMP-compliant propagation of mesenchymal stromal cells. Biomed Mater Eng. 2009;19(4-5):271-6.
23. Schallmoser K, Strunk D. Preparation of pooled human platelet lysate (pHPL) as an efficient supplement for animal serum-free human stem cell cultures. J Vis Exp. 2009 (32).
24. Horn P, Bokermann G, Cholewa D, et al. Impact of individual platelet lysates on isolation and growth of human mesenchymal stromal cells. Cytotherapy. 2010 Jul 22.
25. Centeno CJ. Science Writer FAQs: RSI; 2010.
26. Centeno CJ, Schultz JR, Cheever M, Freeman M, Faulkner BA. Safety and Complications Reporting Update on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique: The Centeno-Schultz Clinic; Broomfield, Colorado, USA; 2010.
27. Khatod M, Inacio M, Paxton EW, et al. Knee replacement: epidemiology, outcomes, and trends in Southern California: 17,080 replacements from 1995 through 2004. Acta Orthop. 2008 Dec;79(6):812-9.
28. Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther. 2010 Mar;5(1):81-93.
29. Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010 Jun;38(6):1110-6.
HB is a 69 year old farmer with moderate loss of cartilage in his ankle (ankle arthritis) who had few options other than an ankle replacement surgery or a triple arthrodesis (ankle fusion surgery). However, he is self employed and the idea of taking that much time off from work on crutches didn’t fit his active lifestyle. Instead, he opted for the re-injection of his own stem cells using a same day procedure. Stem cells were taken from the back of his hip, processed in our clinic lab, and re-injected back into the ankle under x-ray and ultrasound guidance. He is now a few months out from that injection. He reports 100% relief of the pain and here are his words as of this morning:
“I want to thank you for making my ankle pain free with the first injection. I received the first injection the end of August and by the end of September and all of October my ankle has been pain free. I have been able to climb up and down our tractors, combine, and trucks, harvest our Milo crop, swath our hay, make over 400 round bales (6′ tall x 5′ wide) and then load and haul the hay our of the field, which has required my left foot to push on clutches for thousands of times, beside walking and climbing up and down the equipment.”