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Intramyocardial Transplantation of Umbilical Cord Mesenchymal Stromal Cells in Chronic Ischemic Cardiomyopathy: A Controlled, Randomized Clinical Trial (HUC-HEART Trial)
International Journal of Stem Cells
Published online August 31, 2020;  
© 2020 Korean Society for Stem Cell Research.

A. Tulga Ulus1, Ceren Mungan2, Murat Kurtoglu3, Ferda Topal Celikkan4, Mesut Akyol5, Merve Sucu2, Mustafa Toru6, Serdar Savas Gul7, Ozgur Cinar4, Alp Can4

1Department of Cardiovascular Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey
2Ankara University Biotechnology Institute and Sisbiyotek, Ankara, Turkey
3Cardiovascular Surgery Division, Ankara Guven Hospital, Ankara, Turkey
4Department of Histology and Embryology, Laboratory for Stem Cells and Reproductive Cell Biology, Ankara University Faculty of Medicine, Ankara, Turkey
5Department of Biostatistics, Ankara Yildirim Beyazit University, Ankara, Turkey
6Radiology Division, Ankara Liv Hospital, Ankara, Turkey
7Visart Medical Imaging Center, Ankara, Turkey
Correspondence to: Alp Can
Department of Histology and Embryology, Laboratories for Stem Cells and Reproductive Medicine, Ankara University School of Medicine, Sihhiye, Ankara 06410, Turkey
Tel: +903125958169, Fax: +903123103010
E-mail: alpcan@medicine.ankara.edu.tr
Received May 4, 2020; Revised June 18, 2020; Accepted July 6, 2020.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 (23×106) (n=26) or BM-MNCs (70×107) (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.
Keywords : Bone marrow MSC, Clinical trial, Ischemic cardiomyopathy, Stem cell therapy, Umbilical cord MSC