European Knee Meniscus Injury Pilot Trial to Evaluate Cytori Cell Therapy Begins


Cytori Therapeutics is a cell therapy company that is in the process of developing cell therapies from a patient’s own fat tissue that can potentially treat a variety of medical conditions. To date, the preclinical studies and clinical trials suggest that their Cytori Cell Therapy can improve blood flow, modulate the immune system, and facilitating wound repair.

Recently, Cytori has announced that it has enrolled its first patients in an ambitious clinical trial that will test their stem cell product in patients undergoing surgery for traumatic injuries to the meniscus of the knee.  The meniscus is a wedge of cartilage on either side of the knee joint that acts a a shock absorber between the femur and the head of the tibia.

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Ramon Cugat, who is the Co-Director of the Orthopedic Institute, Hospital Quiron Barcelona, Spain, is the principal investigator for this trial. Dr. Cugat serves as an orthopedic surgeon at Hospital Quiron Barcelona. This trial will test the ability of Cytori Cell Therapy to heal the meniscus and is being conducted in parallel with a similar trial that is testing the Cytori Cell Therapy as a treatment for anterior cruciate ligament (ACL) repairs. The patients treated with Cytori Cell Therapy for ACL repairs are still being evaluated, but to date, no safety related concerns have emerged and the patients seem to have improved. These preliminary results were presented at the Barcelona Knee Symposium in November 2014.

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“Dr. Cugat is a leading expert in treating traumatic knee injuries in elite athletes,” said Dr. Marc H. Hedrick, President and CEO of Cytori Therapeutics. “These trials are important to Cytori because, at minimal cost to us, they provide additional clinical evidence that our therapy can be safely used in treating a multitude of knee conditions.”

The meniscus trial is a two-center, phase I study that will assess the safety and efficacy of Cytori’s ECCM-50 adipose-derived regenerative cell therapy in meniscus repair. In this trial, up to 60 patients who have had meniscus surgery to repair the meniscus will receive injection of the cells directly into the meniscus. Each patient will be evaluated by several clinical read outs that assess the recovery of the patient after meniscus surgery. As in the case of the ACL repair study, the goal of this trial is to determine if Cytori Cell Therapy can be safely delivered to the meniscus and whether efficacy can be observed.

“Tears to the meniscus are problematic injuries for active individuals, particularly athletes. Based on the early results from a recent series of 20 patients treated for complete anterior cruciate ligament injuries, we are eager to evaluate whether augmentation surgery with Cytori Cell Therapy will lead to quicker and more complete healing,” said Dr. Cugat.

Injected patients will fill out a patient questionnaire that assesses knee pain, function and activity, This questionnaire is called the Knee Injury and Osteoarthritis Outcome Score (KOOS), but patients will also be physically examined to ascertain the extent of their knee function and the degree of their movement, with or without pain. Patients will be given a visual analogue score to assess knee pain, and knee function will be assessed by the Lysholm Knee Scoring Scale, Tegner Activity Scale, and the Lower Extremity Functional Scale. Each patient will also have their knees examined by Magnetic Resonance Imaging (MRI) in order to examine the structural integrity of their meniscus. These assessments will be taken before and 60, 90, 180 and 365 days after surgery and the MRIs will be done before and at 90, 180 and 365 days after surgery.

The preliminary results of the ACL study showed that the Cytori strategy was feasible and did not result in any significant safety issues above that seen with a standard small volume liposuction. All the injected patients recovered without any complications. The results of the ACL trial were compared to a historical control group of patients who had the same surgical procedure by the same surgical team but without other interventions. Overall, the patient’s recovery from pain and their ability to return to daily activities was accelerated as a result of the therapeutic enriched bone-patellar tendon-bone transplant. Both the patient questionnaires and serial MRI scans of the knees following cell therapy were consistent with accelerated healing of the graft. Presently, Dr. Cugat and his coworkers are obtaining one year follow-up information on the treated patients and they will report their data in a peer-reviewed journal in the future.

ACL and meniscus tears are among the most common sports-related knee injuries and unfortunately, these two injuries often are sustained simultaneously. According to the American Academy of Orthopedic Surgeons, ACL injuries have an annual incidence of more than 200,000 cases with nearly half undergoing surgical reconstruction. Further, an estimated 850,000 patients undergo surgical procedures to address meniscus injuries each year.

Fat-Based Stem Cells in the PRECISE Trial Stabilizes Exercise Performance in Chronic Heart Disease Patients


Cytori Therapeutics has announced the publication of safety and efficacy data from a 36-month European clinical trial of Cytori Cell Therapy in patients with chronic ischemic heart failure. Final data from the Company’s PRECISE trial, a 27-patient, prospective, randomized, double-blind, placebo-controlled, feasibility trial (Phase I/IIA), demonstrated statistically significant differences in cardiac functional capacity between treated and placebo groups.

Their research will appear in the upcoming issue of the American Heart Journal. Cytori Cell Therapy is a mixed population of adipose derived regenerative cells (ADRCs™) extracted from a patient’s own adipose tissue using Cytori’s proprietary Celution® System.

“The PRECISE trial is the first-in-man trial involving the myocardial injection of ADRCs for heart disease,” said Dr. Emerson Perin , Co-Principal Investigator of the trial. “By demonstrating a strong safety profile and suggesting that the use of ADRCs may preserve functional capacity, the data indicates that this therapy may have meaningful impacts on the lives of these very sick patients.”

This particular publication was co-authored by trial investigators Drs. Emerson C. Perin at Texas Heart Institute, Francisco Fernández-Avilés at Hospital Universitario Gregorio Marañón and others. This clinical trial shows that the procedure was safe, feasible and showed indications of a favorable benefit to the patients who received it. The study demonstrated that fat harvest through liposuction could be performed safely in cardiac patients. Exercise capacity as reflected by maximum oxygen consumption (MVO2) during treadmill testing, a reflection of cardiac functional capacity, was sustained in the ADRC treated group but declined in the placebo group at 6 and 18 months. Statistically significant differences were observed between the two groups.

“These results supported the design of the ongoing U.S. Phase II ATHENA trial that is evaluating a similar patient population,” said Steven Kesten , M.D., Chief Medical Officer for Cytori. “We are encouraged by the sustained effects in functional endpoints, particularly MVO2, which is a relevant clinical endpoint in heart disease, and is an aid in directing treatment options, such as assist devices or heart transplant. We look forward to reporting the initial six-month results from the ATHENA trial.”

Additionally, other data trends in this study suggest that ADRC therapy may have a modest beneficial effect in stabilization of the heart scar tissue. To understand the meaning of this benefit, remember that ischemic heart disease might also be known as coronary artery disease (CAD), atherosclerotic heart disease, or coronary heart disease. Ischemic Heart Disease is the most common type of heart disease and cause of heart attacks. This disease is typically caused by plaque build up along the inner walls of the arteries of the heart, which leads to narrowing of the arteries and reduction of blood flow to the heart. After a heart attack, the region of the heart that was deprived of oxygen for a period time dies and the dead heart muscle tissue is replaced by scar tissue that contracts over time, but does not contract or conduct heartbeat impulses. In this study, the scar mass of the left ventricle remained consistent in ADRC-treated patients at six months compared to an increase in control patients. This suggests that ADRCs may prevent scar tissue from increasing. Other endpoints such as ventricular volumes and ejection fraction showed inconsistent findings.

In the PRECISE trial, all patients were treated with standard-of-care and subsequently underwent a liposuction procedure. Each patient’s adipose tissue was processed using Cytori’s proprietary Celution® System to prepare the cell therapy. Cells (n=21) or placebo (n=6) were injected into areas of the heart muscle that were severely damaged but still viable and reversible using the NOGA XP System.

Cytori is currently enrolling patients in the U.S. ATHENA and ATHENA II trials, both 45 patient prospective, randomized, double-blind, placebo-controlled trials investigating a lower and a higher dose, respectively, of Cytori Cell Therapy in a similar patient population as PRECISE.

The PRECISE study is a small study, but the fact that it was double-blinded and placebo controlled makes it an important study. The experimental group showed a clear stabilization of maximum oxygen consumption as opposed to the control group, whose exercise tolerance decreased during the course of the trial. This is potentially significant.  The ADRCs could be preventing the heart from enlarging as a result of working harder.

Questions, however, remain.  For example, is this a short-term effect or does it maintain its effect over the long-term period? To answer that, patient follow-up is necessary. Second, the other physiological parameters showed confusing outcomes (ejection fraction, end-diastolic volume, and so on).  If the ADRCs are truly helping the heart function better, then why don’t the physiological parameters used to measure heart function show some semblance of improvement?  The stabilization of the maximum oxygen consumption stabilization might not mean much in retrospect if it is short-term.

A larger trial like the ATHENA study will be more powerful. Hopefully these PRECISE patients will be followed and examined several years after the treatment to determine the duration of the ADR-provided benefits.

ATHENA Trial Tests Fat-Derived Stem Cells as a Treatment for Heart Failure


The FDA-approved ATHENA trial is the brainchild of stem cell researchers at the Texas Heart Institute at St. Luke’s Episcopal Hospital. The ATHENA trial is the first trial in the United States to examine the efficacy of adipose-derived regenerative cells or ADRCs as a treatment for a severe form of heart failure.

To harvest ADRCs, Texas Heart Institute researchers used a technique that was developed by Cytori Therapeutics, which is a biotechnology company that specializes in cell-based regenerative therapies. Previous clinical trials in Europe strongly suggest that such ADR-based therapies are quite safe and feasible. To date, physicians are the Texas Heart Institute have treated six patients as a part of the ATHENA trial.

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James Willerson, the president and medical director of the Texas Heart Institute, is the principal investigator in the ATHENA trial. Willerson said, “We have found that body fat tissue is a valuable source of regenerative stem cells that are relatively easy to access. We have high hopes for the therapeutic promise of this research and believe that it will lead quickly to larger trials.”

The subjects for the ATHENA trial are patients who suffer from chronic heart failure due to coronary heart disease. Coronary heart disease results from blockage of the coronary vessels and feed the heart muscle and limits the oxygen supply to the heart muscle, and consequently, the pumping activity of the heart muscle. Data from the American Heart Association reveals that there are about 5.1 million Americans who currently live with heart failure, and in many cases, the only viable treatment is a left ventricular assist device (LVAD) or a heart transplant. Unfortunately, there are only about 2,200 heart transplants a year due to a severe shortage of organs.

Coronary artery disease

Patients who are enrolled in the ATHENA trials are randomized and some will receive a placebo treatment and others will receive the experimental treatment. All patients will undergo liposuction in order to remove adipose or fat tissue. Processing of the fat tissue isolates the ADRCs, and the experimental patients will have these cells injected directly into their heart muscle, but the placebo patients will receive injections of culture medium or saline that contains no cells. ATHENA will measure several data endpoints that include objective measures of heart function, exercise capacity, and questionnaires that assess the symptoms and health-related quality-of-life.

The US trial will enroll a total of 45 patients at several centers around the country and these centers include the Texas Heart Institute, Minneapolis Heart Institute, Scripps Green Hospital in San Diego, CA, the University of Florida at Gainesville, and Cardiology P.C. in Birmingham. Patients are being enrolled.

Healthline has recently compiled the statistics on heart disease in an impressive and colorful manner at this link.