Mesoblast MPCs Improve Heart Function in Patients with Congestive Heart Failure


Mesoblast Limited is a biotechology company with a singular interest in developing cell-based, regenerative therapies to treat some rather common, but severe ailments. Mesoblast has a proprietary cell system based on specialized cells known as mesenchymal lineage adult stem cells. These mesenchymal lineage adult stem cells (MLASCs) are being designed to serve as ‘off-the-shelf’ cell products for treating heart conditions, orthopedic disorders, immunologic/inflammatory disorders and cancer.

Mesoblast has recently released the results of a Phase 2 clinical trial that utilized their therapeutic product MPC-150-IM and tested it in patients with chronic congestive heart failure. The results of this study were published in the journal Circulation Research, a high-impact journal of the American Heart Association.

Patients who suffer from advanced heart failure have a poor long-term prognosis and they also have few therapeutic options. The pumping power of their hearts is weaker than normal, and the blood moves through the heart and body at a slower than normal rate. Consequently, fluid pressure in the heart increases and the chambers of the heart respond by stretching to hold more blood to pump through the body or by thickening and becoming stiff. This helps to keep the blood moving, but the heart muscle walls may eventually weaken and become unable to pump as efficiently. The kidneys respond by causing the body to retain fluid (water) and salt, and if the fluid builds up in the arms, legs, ankles, feet, lungs, or other organs, the body becomes congested, and congestive heart failure is the term used to describe the condition.

Mesoblast decided to test their proprietary Mesenchymal Precursor Cells (MPCs) to potentially induce heart muscle repair, stimulate new blood vessel growth, decrease cell death and reduce scar formation. Earlier studies established that MPCs are safe to give to heart patients. This new study examined the ability of these cells to improve heart function in patients with congestive heart failure.

In this study, 60-patients were subjected to a blinded, placebo-controlled trial. MPCs were injected directly into the heart muscle. One of the Primary Endpoints of this study was safety.

Patients included those with ischemic or non-ischemic heart failure (due to left ventricular systolic dysfunction), and in both groups, MPC injections were feasible and safe. There was a similar incidence of adverse events across all control and treatment groups. The patients who were treated with MPCs did not show any clinically significant immune response again the injected MPCs.

When it came to the main Secondary Efficacy Endpoints, patients who were treated with the highest MPC dose showed the greatest improvement in left ventricular remodeling compared to controls as evidenced by significant reductions in Left Ventricular End Systolic Volume (LVESV; p=0.015), and Left Ventricular End Diastolic Volume (LVEDV; p=0.02), 6 months after the treatment. LVESV and LVEDV increase as the heart gets weaker, but in these patients, the LVESV and LVEDV decreased. There were also parallel improvements in ejection fraction, but these improvements were not statistically significant. Patients treated with the highest dose of MPCs also showed the greatest improvement in functional exercise capacity compared to controls (p=0.062) 12 months after receiving their treatments.

Finally, in a post-hoc analysis of all patients 36 months after treatment, patients treated with MPCs showed significantly lower incidence of major adverse cardiac events when compared to the control group (0% vs 33% HF-MACE by Kaplan-Meier, p=0.026 by log-rank).

In their article, entitled ‘A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Non-Ischemic Heart Failure’, the authors concluded that high-dose MPC treatment seems to reduce heart failure-related major adverse cardiovascular events and provide beneficial effects on adverse left ventricular remodeling.

Lead author and investigator Dr Emerson C. Perin, Director, Research in Cardiovascular Medicine and Medical Director of the Stem Cell Center at the Texas Heart Institute, said: “The findings from this trial are very encouraging and suggest that a high-dose of Mesoblast’s allogeneic cell-based therapy may decrease major clinical events associated with progressive heart failure for at least three years, including repeated hospitalizations or death.

“These effects appear to be due to the ability of these cells to positively impact on adverse cardiac remodeling associated with chronic heart failure. If these results are confirmed in the ongoing Phase 3 trial currently recruiting at our institution and elsewhere, this new therapy has the potential to change the paradigm for the management of patients with advanced heart failure and a high risk of hospitalization and death,” Dr Perin added.

A randomized, placebo-controlled Phase 3 trial using Mesoblast’s high-dose MPC 150M is being conducted by Mesoblast’s development and its commercial partner, Teva Pharmaceutical Industries Ltd. Presently, this study is actively enrolling patients across multiple clinical sites in North America.

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Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).