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Human Umbilical Cord Mesenchymal Stromal Cell Transplantation in Myocardial Ischemia (HUC-HEART Trial). A Study Protocol of a Phase 1/2, Controlled and Randomized Trial in Combination with Coronary Artery Bypass Grafting

Abstract

Mesenchymal stem cells (MSCs), which may be obtained from the bone marrow, have been studied for more than a decade in the setting of coronary artery disease (CAD). Adipose tissue-derived MSCs have recently come into focus and are being tested in a series of clinical trials. MSC-like cells have also been derived from a variety of sources, including umbilical cord stroma, or HUC-MSCs. The HUC-HEART trail (ClinicalTrials.gov Identifier: NCT02323477) is a phase 1/2, controlled, multicenter, randomized clinical study of the intramyocardial delivery of allogeneic HUC-MSCs in patients with chronic ischemic cardiomyopathy. A total of 79 patients (ages 30–80) with left ventricle ejection fractions ranging between 25 and 45 % will be randomized in a 2:1:1 pattern in order to receive an intramyocardial injection of either HUC-MSCs or autologous bone marrow-derived mononuclear cells (BM-MNCs) in combination with coronary arterial bypass grafting (CABG) surgery. The control group of patients will receive no cells and undergo CABG alone. Human HUC-MSCs will be isolated, propagated and banked in accordance with a cGMP protocol, whereas the autologous BM-MNCs will be isolated via aspiration from the iliac crest and subsequently process in a closed-circuit cell purification system shortly before cell transplantation. The cell injections will be implemented in 10 peri-infarct areas. Baseline and post-transplantation outcome measures will be primarily utilized to test both the safety and the efficacy of the administered cells for up to 12 months.

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Acknowledgments

This project was supported by SANTEZ, Project # 0741-STZ-2014 (AC, ATU, OC) and the ATIGEN-CELL Technologies Cell and Gene Center (ME).

Conflict of Interest

One of the authors (ME) works as a scientist for stem cell manufacturing at an ATIGEN-CELL cell production facility. The remaining authors have no conflicts of interest to declare regarding the publication of this manuscript.

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Correspondence to Alp Can.

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Can, A., Ulus, A.T., Cinar, O. et al. Human Umbilical Cord Mesenchymal Stromal Cell Transplantation in Myocardial Ischemia (HUC-HEART Trial). A Study Protocol of a Phase 1/2, Controlled and Randomized Trial in Combination with Coronary Artery Bypass Grafting. Stem Cell Rev and Rep 11, 752–760 (2015). https://doi.org/10.1007/s12015-015-9601-0

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  • DOI: https://doi.org/10.1007/s12015-015-9601-0

Keywords

  • Umbilical cord MSC
  • Bone marrow MNC
  • Ischemic cardiomyopathy
  • Regenerative medicine
  • Stem cell therapy
  • Clinical trial