Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary Left Ventricular Assist Devices

Abstract

Background Allogeneic mesenchymal precursor cells (MPC) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy. Methods and Results In this multi-center, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25M MPCs or medium during LVAD implantation. The primary safety endpoint was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days post-randomization). Key efficacy endpoints were functional status and ventricular function, while temporarily weaned from LVAD support (90 days post-randomization). Patients were followed until transplant or 12 months post-randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean LVEF 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (p=0.24); the posterior probability that MPCs increased the likelihood of successful weaning is 93%. At 90 days, 3 deaths occurred in control and none in MPC patients. Mean LVEF following successful wean was 24.0% (MPC=10) and 22.5% (Control=2) (p=0.56). At 12 months, 30% of MPC and 40% of control patients were successfully temporarily weaned from LVAD support (p=0.69) and 6 deaths occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months. Conclusions In this preliminary trial, administration of MPCs appeared to be safe and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support. Clinical Trial Registration Information ClinicalTrials.gov. Identifier: NCT01442129.

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

“…Although MSCs, with or without endothelial cells, have already been used by others to promote vascularization of implanted constructs and ischemic tissues in both preclinical and clinical settings [47,[65][66][67][68][69], the optimal MSC yielding the maximal therapeutic angiogenic response has yet to be determined. Results presented in this study and elsewhere suggest that thymus MSCs may be a promising candidate for therapeutic use [6,7].…”

The Future of Heart Failure Diagnosis, Therapy, and Management

“…47 Most examples of recovery occur in young patients with short duration of illness without coronary artery disease. Ventricular assist device support does provide a sturdy platform on which to try multiple approaches to reengineer functional myocardium, 51 …”

New Management Strategies in Heart Failure

“…72 Neurohormonal blockade remains a cornerstone of management in conjunction with mechanical support to unload a failing heart and promote positive remodeling. 73 The use of mesenchymal precursor cells may be a promising adjunctive therapy in this regard as recent data from Ascheim et al 74 support.…”