CardioCell, a global biotechnology company that explores therapeutic applications of unique, patented, ischemia-tolerant mesenchymal stem cells (itMSCs) manufactured under cGMP conditions, announces two new clinical trials using its allogeneic stem-cell therapy to treat subjects with acute myocardial infarction (AMI), a problem facing more than 1.26 million Americans annually. In the U.S., CardioCell is initiating a phase IIa AMI clinical trial to evaluate the clinical safety and efficacy of its itMSCs. In addition, the Ministry of Health in Kazakhstan is beginning a phase III AMI clinical trial on the intravenous administration of CardioCell’s itMSCs, based on the efficacy and safety found in phase II clinical trials.
Only CardioCell’s AMI therapies feature itMSCs, which are exclusively licensed from CardioCell’s parent company Stemedica Cell Technologies. Unlike all other MSCs—which are grown under normoxic conditions—itMSCs are grown under hypoxic conditions that more closely resemble the environment in which they live in the body. These bone-marrow-derived, allogeneic, mesenchymal stem cells are unique because they are grown under chronic hypoxic conditions and are ischemia-tolerant. Compared to other MSCs, itMSCs secrete higher levels of growth factors usually associated with angiogenesis and healing. The current studies have been designed to help determine if CardioCell’s itMSC-based therapies stimulate a regenerative response in AMI patients.
“Our studies target AMI patients who have depressed left ventricular ejection fraction (LVEF), which makes them prone to developing extensive scarring and therefore to the development of chronic heart failure,” said Dr. Sergey Sikora, Ph.D., CardioCell’s president and CEO. “CardioCell hopes our itMSC therapies will inhibit the development of extensive scarring and, thus, the occurrence of chronic heart failure in these patients.”
Taking place at Emory University, Sanford Health and Mercy Gilbert Medical Center, CardioCell’s phase IIa AMI trial is a double-blinded, multicenter, randomized study to assess the safety, tolerability and preliminary clinical efficacy of a single, intravenous dose of allogeneic mesenchymal bone-marrow cells to subjects with ST segment-elevation myocardial infarction (STEMI).
“While stem-cell therapy for cardiovascular disease is nothing new, CardioCell is bringing to the field a new type of stem-cell technology that has the possibility of being more effective than other AMI treatments,” said Dr. Stephen Epstein, MedStar Heart Institute’s director of Translational and Vascular Biology Research and CardioCell’s scientific advisory board chair. “Evidence exists demonstrating that MSCs grown under hypoxic conditions express higher levels of molecules associated with angiogenesis and healing processes. There also is evidence indicating they migrate with greater avidity to various cytokines and growth factors and, most importantly, home more robustly to ischemic tissue. Studies like those underway using CardioCell’s technology are designed to determine if we can evoke a more potent healing response that will reduce the extent of myocardial cell death occurring during AMI and thereby decrease the amount of scar tissue resulting from the infarct. A therapy that could achieve this would have a major beneficial impact in reducing the occurrence of chronic heart failure.”
In addition to the U.S. study, Kazakhstan’s National Scientific Medical Center is conducting a phase III AMI clinical trial using CardioCell’s itMSCs, which are sponsored by local licensee Altaco. This study, “Intravenous Administration of itMSCs for AMI Patients,” is proceeding based on a completed phase II efficacy and safety study. Results for that phase II study are preliminary because the sample group was so small, but the findings demonstrated statistically significant elevation (more than 12% over the control group) in LVEF and reduction in inflammation, as suggested by lower CRP (C-reactive protein) levels in treatment verse control groups.
Thus, Dr. Daniyar Jumaniyazov, M.D., Ph.D., principal investigator in Kazakhstan clinical trials, said, “In our clinical phase II trial for patients with AMI, treatment using itMSCs improved global and local myocardial function and normalized systolic and diastolic left ventricular filling, as compared to the control group. We are encouraged by these results and look forward to confirming them in a phase III study.”
CardioCell’s treatment is the first to apply itMSC therapies for cardiovascular indications like AMI, chronic heart failure and peripheral artery disease. Manufactured by CardioCell’s parent company Stemedica and approved for use in clinical trials, itMSCs are manufactured under Stemedica’s patented, continuous-low-oxygen conditions and proprietary media, which provide itMSCs’ unique benefits: increased potency, safety and scalability. itMSCs differ from competing MSCs in two key areas. itMSCs demonstrate increased migratory ability towards the place of injury, and they show increased secretion of growth and transcription factors (e.g., VEGF, FGF and HIF-1), as demonstrated in a peer-reviewed publication. This can potentially lead to improved regenerative abilities of itMSCs. In addition, itMSCs have significantly fewer HLA-DR receptors on the cell surface than normal MSCs, which might reduce the propensity to cause immune responses. As another benefit, itMSCs are highly scalable. A single donor specimen can currently yield about 1 million patient treatments, and this number is expected to grow to 10 million once full robotization of Stemedica’s facility is complete.