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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

Stem Cell Reviews and Reports volume 11, pages 752–760 (2015)Cite this article

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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Authors and Affiliations

  1. Department of Histology and Embryology, Laboratory for Stem Cells and Reproductive Cell Biology, Ankara University School of Medicine, Ankara, Turkey

    Alp Can, Ozgur Cinar & Ferda Topal Celikkan

  2. Department of Cardiovascular Surgery, Hacettepe University School of Medicine, Ankara, Turkey

    Ahmet Tulga Ulus

  3. Ministry of Health, Cardiovascular Surgery Division, Ankara, Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey

    Erdal Simsek

  4. Department of Biostatistics, Yildirim Beyazit University, Ankara, Turkey

    Mesut Akyol

  5. Department of Cardiology, Hacettepe University School of Medicine, Ankara, Turkey

    Ugur Canpolat

  6. ATIGEN-CELL Technology, Trabzon, Turkey

    Murat Erturk

  7. Ob-Gyn Division, Ministry of Health Dr. Sami Ulus Maternity Hospital, Ankara, Turkey

    Fadil Kara

  8. Department of Hematology, Ankara University School of Medicine, Ankara, Turkey

    Osman Ilhan

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  1. Alp Can
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  2. Ahmet Tulga Ulus
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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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Keywords

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