Delayed Bone Marrow Transplantations Following Heart Attacks Is Safe But Not Effective

The LateTIME study (Transplantation In Myocardial Infarction Evaluation) rigorously examined the safety and effectiveness of whole bone marrow cell transplantations into the heart after a heart attack. This study definitively established the safety of this procedure, but it was not able to demonstrate the effectiveness of it.

LateTIME study participants received bone marrow transplants two-three weeks after suffering from a heart attack. Between July 2008 and February 2011, 87 people who had suffered heart attacks were enrolled in the LateTIME study. All patients had undergone cardiac procedures to open blocked arteries, and had moderate to severe impairment in their left ventricles, the heart chamber that pumps oxygen-rich blood from the heart to the systemic circulation where the blood flows through the body. All participants had stem cells taken from bone marrow in their hip for processing. LateTIME researchers developed a standardized method of processing and purifying bone marrow stem cells, and this was the first BMC trial to provide a uniform dose of BMCs to each participant. The study also randomly assigned the participants to receive either their purified BMCs or inactive (placebo) cells.

Several previous studies have suggested that injecting BMCs into the heart can improve cardiac function following a heart attack and perhaps reduce the need for future hospitalizations and heart surgeries. In contrast to LateTIME, earlier studies delivered BMCs within a few days of the heart attack. In many cases, a patient will not be able to get such immediate treatment, due to poor health following a heart attack or because the hospital providing care doesn’t have a stem cell therapy program.

“Although treatment and survival following a heart attack have improved over the years, the risk of heart failure following a heart attack has not decreased,” said Susan B. Shurin, M.D., acting director of the NHLBI. “Stem cell therapy is a promising direction for repairing the damage done by a heart attack. We do not fully understand the optimal use of these cells; studies like LateTIME will help us understand how to perform and monitor these procedures.”

After six months, improvement of heart function was assessed by measuring the percentage of blood that gets pumped out of the left ventricle during each contraction (left-ventricular ejection fraction, or LVEF) by cardiac MRI. There were no significant differences between the change in LVEF readings between baseline and six months in the BMC (from 48.7 percent to 49.2 percent) or placebo (from 45.3 percent to 48.8 percent) groups.

“This does not mean that stem cell therapy will only work if done immediately following a heart attack or that later beneficial effects on clinical outcomes won’t emerge,” noted Lemuel A. Moyé , M.D., Ph.D., professor of biostatistics at the University of Texas School of Public Health, Houston, and a LateTIME researcher. “Many factors influence how the heart responds to stem cells, which highlights the critical need to continue rigorous tracking studies in this area.” Moyé also added that the health of the study participants will continue to be evaluated for two years, so the BMC therapy may yet demonstrate health benefits such as a lower risk of subsequent heart attacks or heart failure, in which the heart cannot pump enough blood to meet the body’s needs.

LateTIME is one of three heart stem cell trials being undertaken by the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network. The other trials under way by this multicenter consortium are TIME, which compares the effectiveness of stem cell therapy delivered at three days versus seven days following a heart attack, and FOCUS, which examines stem cell therapy in people with chronic heart failure.

This study and several others seem to establish that whole bone marrow is simply not as effective for treating heart attack patients as specific stem cell populations. Bone marrow stem cells are a very heterogeneous population, and specific populations of bone marrow stem cells must be isolated, expanded, and conditioned for heart muscle/blood vessel differentiation before they can be used. These specific stem cell populations are almost certainly much more effective than whole bone marrow, which contains a variety of cells that almost certainly cannot survive in the oxygen-poor environment of the heart after a heart attack.

Centeno Stem Cell Treatment Featured in ESPN Magazine

Christopher Centeno runs a stem-cell based orthopedic clinic in Broomfield, Colorado.  In 2010, NFL defensive end Jarvis Green visited Centeno after Green had experienced two failed knee surgeries. Green faced the end of his eight-year career with the New England Patriots.  Then Centeno performed his Regenexx-C procedure on Green, and he is a new man.

Shortly after receiving his stem cell treatment, Green was back in the NFL. “Before, I couldn’t walk up the stairs,” Green told The Mag. “Three weeks later, I went to an NFL training camp and didn’t miss a day.” Green’s procedure has been featured on and in the ESPN Magazine.  Green’s football career has been saved and he is sold on stem cell treatments.

Unfortunately, not everyone is happy about Green’s successful recovery and not everyone is applauding Centeno’s procedure.  The first unhappy onlooker is the United States Food and Drug Administration (FDA).  In August 2010, the FDA filed a federal injunction to prevent Centeno from culturing stem cells from patients.  The FDA claims that Centeno was “adulterating” blood in a way that turned it into an unapproved new drug.  Centeno, who still provides same-day stem cell procedures, has spent $500,000 fighting the agency’s controversial opinion and even more money moving his culturing operation to a new clinic offshore in the Cayman Islands where the FDA cannot hassle him.  Centeno told the ESPN Magazine, “The FDA has pushed this therapy out of the U.S.”

First of all, the FDA’s claim is bogus, bordering on stupid.  Regenexx takes the bone marrow stem cells (mesenchymal stem cells) and cultures them for about 6 weeks.  This is part of what Regenexx calls the “Regenexx-C” procedure.  These cultured and expanded mesenchymal stem cells are precisely applied to the joint, tendon or cartilage surface that requires repair.  Then the stem cells are allowed to work their healing ways. Somehow, the FDA thinks that culturing mesenchymal stem cells and expanding them in culture sufficiently changes them so that they now constitute a drug, and therefore the FDA gets to regulate it.  Excuse me FDA, BUT IT’S THE PATIENT’S CELLS.  BUTT OUT!!!!  Seriously folks, this is just one of umpteen hundred some-odd stories of the FDA’s stupidity, and overstepping their bounds.  Our FDA needs serious reformation and they need to set discrete limits on what they can and can’t regulate.  How can these naturopathic quacks give all manner of herbal concoctions to their patients without the FDA making a sound while Centeno gives people their own cells and the FDA says that they are getting an unapproved drug?  Clearly this is bureaucratic nonsense.

The secondly unhappy camper is Theodore Friedmann, a geneticist at the University of California, San Diego who heads the World Anti-Doping Agency’s (WADA) gene doping panel and has been given the job of advising WADA on stem cell policy.  Friedmann wrote, “There’s very little evidence that bone marrow stem cells taken from one site and injected into another will do anything. . . The most likely outcome is that if you put stem cells in places that are unfamiliar to them, like a knee or shoulder, most of them will just die.”  Both of these statements drip with ignorance.  In the case of orthopedic usages of mesenchymal stem cells, there is a copious literature of experiments on laboratory animals that shows that extracted mesenchymal stem cells from bone marrow can help heal joint abnormalities (CJ Centeno & SJ Faulkner, “Regenerative Orthopedics” in Advances in Regenerative Medicine, edited by Sabine Wislet-Grendebien,  InTech, 2011, 349-362).  Secondly, there is a gradually accumulating corpus of literature that shows that the use of expanded mesenchymal stem cells from bone marrow reduces symptoms in patients with hip or knee problems (Centeno et al., Pain Physician 9(3): 253-6; Centeno et al., Pain Physician 11(3): 343-53; Centeno et al., Medical Hypotheses 71(6): 900-8), and causes few side effects (Centeno et al., Current Stem Cell Research Therapy 5(1): 81-93).  Centeno and his group have tracked over 339 patients who have received his procedure for up to three years and none of them have shown any tumors or ectopic tissue growth.  Likewise and 11-year study of 45 different knees in 41 different patients that were treated with their own bone marrow mesenchymal stem cells showed effective treatment of knee injuries and a lack of side effects (Wakitani, et al., Journal of Tissue Engineering and Regenerative Medicine 5(2): 146-150).  Another study examined cultured bone marrow mesenchymal stem cells that were reimplanted into the knees of patients with articular cartilage defects in platelet-rich fibrin.  The results showed evidence of healed cartilage in most of the patients 12 months after the procedure (Haleem, et al., Cartilage 1(4): 253-261).  So much for “there’s very little evidence that bone marrow stem cells taken from one site and injected into another will do anything.”

Friedmann’s second statement, “The most likely outcome is that if you put stem cells in places that are unfamiliar to them, like a knee or shoulder, most of them will just die,” shows that he clearly does not understand the procedure used by Centeno and others.  Regenexx uses MRI-guided injection systems to precisely implant stem cells at the location where they are needed.  Centeno himself has blasted the use of blind stem cell injections into the knee.  Because the stem cells are delivered to precisely the point of need, they do not move far from the point of injection, and they do what they need to do at the point of injury.  This is a significant part of the success of the Regenexx method, as is the conditioning of the stem cells with platelet-enriched plasma that the FDA erroneously thinks is a drug.  This is not scatter-shot introduction of stem cells into a joint, but it is a genuine point-of-defect delivery of healing stem cells.

All in all, the Regenexx procedure has helped some serious athletes recover the use of their joints and earn their living.  These procedures have been shown to be safe and effective, at least in some patients.  The United States should allow these clinics to run their procedures in the country.  It would provide a significant source of revenue when our economy seriously needs it and to disallow it because of some cock-and-bull-fairytale about cultured mesenchymal stem cells being a drug is a perfect example of the kind of over-regulation that is killing innovation in our country and stripping our economy of the things that can make it great again.  In November we need to go to the pools and throw this present government out on their ears.