Intramyocardial Transplantation of Umbilical Cord Mesenchymal Stromal Cells in Chronic Ischemic Cardiomyopathy: A Controlled, Randomized Clinical Trial (HUC-HEART Trial)

Abstract

Background and Objectives: The HUC-HEART Trial (ClinicalTrials.gov Identifier: NCT02323477) was a controlled, prospective, phase I/II, multicenter, single-blind, three-arm randomized study of intramyocardial delivery of human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) combined with coronary artery bypass-grafting (CABG) in patients with chronic ischemic cardiomyopathy (CIC). The trial aimed to assess (i) the safety and the efficacy of cell transplantation during one-year follow-up, (ii) to compare the efficacy of HUC-MSCs with autologous bone-marrow-derived mononuclear cells (BM-MNCs) in the same clinical settings. Methods and Results: Fifty-four patients who were randomized to receive HUC-MSCs (23×10 6) (n=26) or BM-MNCs (70×10 7) (n=12) in combination with CABG surgery. The control patients (n=16) received no cells/vehicles but CABG intervention. All patients were screened at baseline and 1, 3, 6, 12 months after transplantation. Forty-six (85%) patients completed 12 months follow-up. No short/mid-term adverse events were encountered. Decline in NT-proBNP (baseline∼ 6 months) in both cell-treated groups; an increase in left ventricular ejection fraction (LVEF) (5.4%) and stroke volume (19.7%) were noted (baseline∼6 or 12 months) only in the HUC-MSC group. Decreases were also detected in necrotic myocardium as 2.3% in the control, 4.5% in BM-MNC, and 7.7% in the HUC-MSC groups. The 6-min walking test revealed an increase in the control (14.4%) and HUC-MSC (23.1%) groups. Conclusions: Significant findings directly related to the intramyocardial delivery of HUC-MSCs justified their efficacy in CIC. Stricter patient selection criteria with precisely aligned cell dose and delivery intervals, rigorous follow-up by detailed diagnostic approaches would further help to clarify the responsiveness to the therapy.

Intramyocardial injected human umbilical cord-derived mesenchymal stem cells (HucMSCs) contribute to the recovery of cardiac function and the migration of CD4+ T cells into the infarcted heart via CCL5/CCR5 signaling

“…MSCs, as promising cell candidates for transplantation, have been widely used in various clinical diseases especially ischemic heart diseases [ 15 ]. Recent clinical study demonstrated the safety of intramyocardial transplantation of HucMSCs in patients subjected to chronic ischemic cardiomyopathy by monitoring the incidence of adverse events within the 12 months follow-up period [ 16 ]. In the present study, we firstly evaluated the safety of HucMSCs in vivo.…”

“…Results from preclinical studies indicated the role of HucMSCs in improving the cardiac function in acute rat MI models [ 17 ]. Further randomized controlled trial suggested the significant efficacy of intramyocardial delivery of HucMSCs in chronic ischemic cardiomyopathy [ 16 ]. Consistent with these findings, intramyocardial administration of HucMSCs after MI can significantly improve LVEF and LVFS both on day 7 and 28, and further reduced LVEDV/LVESV and LVEDD/LVESD on day 28 in murine MI models.…”

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases

“…The recently published phase I/II HUC-HEART Trial evaluated safety and efficacy of UC-MSC versus autologous BM-MSC combined with CABG in patients with chronic ischemic cardiomyopathy. After 12 months of follow-up, patients from the UC-MSC group showed an increase in left ventricular ejection fraction and a reduction in the necrotic myocardium area [ 127 ]. However, a similar randomized phase I trial using UC-MSC along with a collagen scaffold in chronic ischemic heart disease patients submitted to CABG have demonstrated that despite the absence of severe adverse effects, patients submitted to cell therapy along with the scaffold or not, had no significant change in fibrotic scar tissue [ 128 ].…”

Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

“…Furthermore, UC-MSC-treated patients exhibit significant improvement in LVEF. In addition, the recently reported HUC-HEART trial compares the effects of UC-MSCs and BMMNCs in ICM patients [ 86 ]. UC-MSCs improve global cardiac function, stroke volume, and 6-min walk distance at 12-month follow-up.…”