Clinical Study Evaluates Healing of Knee Cartilage With Stem Cells

The biotechnology company InGeneron will test its patented Transpose RT system in a clinical study that examined the ability of regenerative cells from a patient’s own fat to enhance cartilage healing after knee surgery.

Qualified patients are being recruited through the Fondren Orthopedic Group in Houston. According to the American Orthopedic Society for Sports Medicine, over 4 million knee arthroscopies are performed worldwide each year. Damaged knee cartilage is very difficult to treat and can lead to chronic pain and long-term disability.

Robert Burke, who is serving as the principal investigator of this clinical study, is an orthopedic surgeon with the Fondren Orthopedic Group in Houston. Burke thinks that stem cells taken from a patient’s own fat may enhance cartilage healing. He studied adding patient-derived regenerative cells to the knee during arthroscopic surgery for particular patients, and compared them to patients who had arthroscopic surgery without added fat-derived stem cells.

Arthroscopic surgery is a common procedure is commonly used to treat damaged cartilage, and the patients who had received arthroscopic surgery were randomly chose to either receive fat-derived stem cells or not receive them. Burke, will then monitor these patients for the next 12 months after surgery to determine if the added cells improved cartilage healing.

According to Burke, “Articular cartilage, the smooth surface covering the joints at the ends of bones, has no good way of healing on its own. The body doesn’t create enough new cartilage of the same type to repair the damage.” Better treatments would use various techniques to help the body make new cartilage.

“Stem cells and other regenerative cells that we can obtain fat have the potential to do that,” said Burke. Such regenerative cells can divide and mature to form several types of cells and tissues. and are found in multiple places in the body. Fat that lies just below the skin is one of the easiest places to obtain stem cells.

The InGeneron Transpose RT System uses a small amount of fat, which is removed and processed to separate out the regenerative cells. The separated adipose tissue-derived mesenchymal stem cells are then immediately placed into the area of damaged cartilage during knee surgery. Once in the knee, these cells may divide to make new cartilage cells.

This kind of biological activity has been seen in laboratory studies and veterinary medicine. However, Burke’s study will be one of the first to test the technology in humans for treating cartilage damage. Like other types of stem cell-based therapies, the treatment is not currently licensed for human use in the United States but it is registered in Europe, Mexico, and other countries. Following the Texas Medical Board’s rules about the use of stem cells for treatment, this study is under the supervision of the research review board at Texas Orthopedic Hospital, where all of the patients will undergo surgeries.

This is a two-year study.

SCIPIO Clinical Trial Shows Remarkable Promise

Scipio Africanus is the name given to a very competent Roman general who defeated that wily Carthaginian general Hannibal at the Second Punic War. SCIPIO, therefore, is a fitting name for a remarkable clinical trial that goes by the longer title: Cardiac Stem Cell Infusion in Patients with Ischemic Cardiomyopathy.  This clinical trial is the brainchild of researchers at the University of Louisville and Brigham and Women’s Hospital, and is the first clinical trial to test the safety and efficacy of heart-based stem cells as treatments for heart attack patients.

SCIPIO researchers isolated and expanded cardiac stem cells (CSCs) from approximately one gram of atrial tissue.  This tissue was taken from heart attack patients during coronary bypass surgery.  CSCs were initially discovered and cultured by scientists in the laboratory of Piero Anversa at Brigham and Women’s Hospital in Boston (see Frati C, et al., Resident cardiac stem cells. Current Pharmaceutical Design. 2011 17(30):3252-7).  CSCs have the capacity to express several heart-specific genes and, in animal studies, can repair the heart after a heart attack.  Anversa’s lab was quite careful to establish that the isolated cardiac stem cells expressed a gene called “c-kit,” which is a marker for these stem cells, and that these cells had good growth potential and were largely uncommitted.  In this case Anversa was quite sure that the cells given to the patients were able to grow, differentiate, and integrate into the heart.

Between three to four months after coronary artery bypass surgery, around one million CSCs were transplanted into the heart of each heart attack patient.  This feature of the clinical trial is known as an  “autologous” stem cell treatment, since each patient received stem cells taken from their own body.  Autologous stem cells treatments minimize the risk of rejection by the patient’s immune system.

Throughout the following year after the stem cell treatment, participating patient’s left ventricles were viewed and their heart function was assessed with echocardiography and magnetic resonance imaging.   To say that the results were encouraging is an understatement.  Before the stem cell treatment, each patient was experiencing a stable decrease in left ventricular function.  There was no change in left ventricular function and functional status in the seven control patients who underwent coronary bypass surgery but did not undergo CSC transplantations.  However, 14 of the 16 patients who received CSCs transplants showed an 8.2% average increase in ejection fraction and a 24% decrease in infarct size.  In eight patients studied one year after the CSC treatments, these benefits not only were sustained, actually increased.  Even more encouraging is the absence of adverse effects, which confirms the overall safety of the CSC treatment.

SCIPIO study author, Dr. John Loughran, said this about the current status of the SCIPIO study: “We have enrolled 20 CSC-treated patients, all of whom have been treated with CSC infusion. The trial is currently closed to enrollment.  All patients are followed at serial time points for 2 years. We are working diligently on the creation of an IND application to the FDA for a Phase 2 clinical trial. We hope for this next investigation to be underway within 2 years.”

Dr. Loughran also noted that the isolation of CSCs from the heart is safe and feasible.  This will allow physicians to also treat heart patients who do not depend on surgery, which turns out to be the majority of heart patients.  A simple heart biopsy could probably provide enough tissue for CSC isolation and expansion in the laboratory.

Roberto Bolli, M.D., Director, Institute for Molecular Cardiology at the University of Louisville, echoed these sentiments:  “Harvesting, culturing and infusing CSCs are not particularly expensive and could be repeated multiple times in the same patient. We have preliminary data suggesting that CSCs can be isolated and expanded from minuscule fragments of cardiac tissue obtained during endomyocardial biopsy, which would make this procedure widely applicable in patients with heart failure.”

There are also possibilities that CSCs can be tested for use as a treatment for other heart-based diseases.