Research Project

Significance

Cardiovascular disease (CVD) is still the primary cause of mortality and morbidity in the Western World. In addition to cardiac pathology and its complex time-dependent evolution, the inherent inability of native cardiomyocytes to regenerate leads to a progressive cumulative cardiac degeneration, exacerbated with increasing age, eventually causing heart failure. Interventional, surgical, or phrarmacological treatment of CVD in Europe exceeds 192 billion Euro and accounts for > 2 million deaths/year. Over the past 16 years, implantation of stem cells (SCs) has provided a methodological pathway that promises tissue regeneration aiming to improve cardiac function following ischemic injury.

Career Development Plan

The short- and long-term objectives of the fellowship target the advancement of the fellow’s career and the diversification of his scientific horizons, to allow him to acquire new research skills in cell and tissue engineering, labeling, bioimaging, within the unique environment of a top institution (U. Oxford). These objectives are summarized in a comprehensive career development plan (CDP).

Scientific Aims

Objective 4: a) To develop complementary and new scientific skills, accumulate personal development skills, through skilling and re-skilling, to reach a position of professional maturity in research.

Objective 1:  a) To develop and validate quantitative 19F-MRI in phantoms; facilitate in vivo cellular migration and engraftment with tracking of labelled CDCs using PFC Nanoparticles (NPs) and emulsions in murine MI.

Objective 2:  To quantify global and regional cardiac functional improvements post-SC administration. b) To assess cellular engraftment and proliferative rate improvements with a novel biodegradable scaffold in murine MI.

Publications

Books

  1. Assessment of Cellular and Organ Function and Dysfunction using Direct and Derived MRI Methodologies (2016). C. Constantinides (Editor). InTech Publications, November 2016.
  2. Protocols and Methodologies in Preclinical and Clinical Cardiac Magnetic Resonance Imaging (2017). C. Constantinides (Editor). Springer-Verlag Publications (published, October 2017).

Book Chapters

  1. C. Constantinides. Cardiac Multinuclear MRI. Constantinides C (Editor), Protocols and Methodologies in Preclinical and Clinical Cardiac Magnetic Resonance Imaging (published, October 2017).

Journal Publications

Published/In Press/Accepted

  1. Molecular and integrative physiological effects of isoflurane anesthesia: the paradigm of cardiovascular studies in rodents using Magnetic Resonance Imaging. Constantinides C, Murphy K. Frontiers of Cardiovascular Physiology, July 2016.
  2. Temporal accumulation and localization of isoflurane in the C57BL/6 mouse and assessment of its potential contamination in 19F MRI with perfluoro-crown‑ether-labeled cardiac progenitor cells at 9.4 T. Constantinides C, Maguire M, Stork L, Swider E, Srinivas M, Carr AC, Schneider JE. JMRI, December 2016.
  3. A performance evaluation of GPU parallelization, space-time adaptive algorithms and their combination for simulating cardiac electrophysiology. Oliveira RS, Rocha BM, Burgarelli D,  Meira M, Constantinides C, dos Santos RW. Int J Num Methods in Biomed Eng (published), June 2017.
  4. Fast, Quantitative, Murine Cardiac 19F MRI/MRS of PFCE-labeled Progenitor Stem Cells and Macrophages at 9.4T. Constantinides C, Mahon M, McNeill E, Carnicer R, Swider E, Srinivas M, Carr C, Schneider J. Plos One (accepted), January 2018.
  5. In Vivo Tracking and 1H/19F MRI of Biodegradable Polyhydroxyalkanoate/Polycaprolactone Blend Scaffolds Seeded with Labeled Cardiac Stem Cells. Constantinides C, Basnett P, Lukasiewicz B, Carnicer R, Swider E, Majid Q, Srinivas M, Carr CA, Roy I. ACS AMI (published), July 2018.
  6. FuGENE. Constantinides C et al. (completed-submitted), November 2017.

Other Publications

Published

  1. Cardiac Image-Based Phenotyping: A Scientific Fairytale or an Emerging Reality? Oxford University Biophysical Society (OUBS) Phenotype, p.18. Constantinides C. June 2016.

Conference Papers and Abstract Publications

Published/Submitted

  1. Effects of Inhalational Isoflurane Anaesthesia on 19F MRS/MRI of the In Vivo Mouse at 9.4T. ISMRM Workshop on Molecular and Cellular MRI: Focus on Integration: Amsterdam, Netherlands, June 2016. Christakis Constantinides, Mahon L. Maguire, Leeanne Stork, Mangala Srinivas, Edyta Swider, Carolyn A. Carr, Jurgen E. Schneider. Amsterdam, Netherlands, #6.
  2. Improvements in the Cellular Uptake of Perfluorocarbon Nanoparticles and 19F MRS/MRI Detectability using the Transfection Agent FuGENE. ISMRM Workshop on Molecular and Cellular MRI: Focus on Integration: Amsterdam, Netherlands, June 2016. Christakis Constantinides, Eileen McNeill, Matt Benson, Raquel Sainz Urruela, Sergi Padilla, Sophia Malandraki-Miller, Mahon L. Maguire, Edyta Swider, Sahar Ghaffari, Mangala Srinivas, Carolyn A. Carr, et al. Amsterdam, Netherlands.
  3. Fast, Quantitative 19F MRI: Optimized Imaging Strategies. ESMRMB 2016, Vienna, Austria, October 2016. Christakis Constantinides, Mahon L. Maguire, Sophia Malandraki-Miller, Edyta Swider, Mangala Srinivas, Carolyn A. Carr, et al. In Proceedings of ESMRMB 2016, Vienna, Austria, #122.
  4. Post-mortem Cardiac and Skeletal Muscle 19F MRI of PFCE-labeled and FuGENE-transfected Cardiac Progenitor Stem Cells in the C57BL/6 Mouse. Christakis Constantinides, Ricardo Carnicer, Mahon L. Maguire, Eileen McNeill, Ayman Haj Al Zen, et al. ISMRM (accepted), Hawaii, May 2017.
  5. Temporal Assessment of In Vitro Survival, Uptake Efficiency, and Fluorescence of Cardiac Stem Cells Labelled with PLGA-PFCE Nanoparticles and Transfected with FuGENE. Christakis Constantinides, Ayman Haj Al Zen, Eileen McNeill, et al. ESMI (accepted), Cologne, Germany, April 2017.
  6. Tracking of PLGA-PFCE-labeled Cardiac Stem Cells Seeded on Novel Biodegradable Poly(3-hydroxyoctanoate) Scaffolds Implanted on the Murine Myocardium using 1H and 19F  MRI/MRS. Chris Constantinides , Ricardo Carnicer Hijazo , Andrew Shaw , Jyoti Patel , Edyta Swider , Mangala Srinivas , and Carolyn Carr. ISMRM 2018, Paris, France, May 2018.
  7. In Vivo Murine Cardiac 19F MRI and Tracking of PFCE- and FuGENE-labeled Progenitor Stem Cells in the C57BL/6 Mouse. Chris Constantinides , Ricardo Carnicer Hijazo , Andrew Shaw , Jyoti Patel , Edyta Swider , Mangala Srinivas , and Carolyn Carr. ISMRM 2018, Paris, France, May 2018.
  8. Comparison of Labeling Capacity for Protamine-sulphate-conjugated and FuGENElabeled Progenitor Cardiac Stem Cells using Perfluorocarbon Nanoparticle Labels for In Vivo Murine Cardiac 19F MRI/MRS. Chris Constantinides , Akhilesh Rai , Mangala Srinivas , Lino Ferreira , and Carolyn Carr. ISMRM 2018, Paris, France, May 2018.

Honors and Awards

  1. Member of the InTech Editorial Advisory Board (Medical Diagnostics, Engineering, and Telemedicine), 9 May, 2015 (upon invitation), 2016-2017.
  2. Micro Travel Grant, Marie Sklodowska Curie Association (December 2016) for attendance to the 2017 European Society of Molecular Imaging Conference, Cologne, Germany.
  3. Supplementary funding, Metochemie Ltd., Limassol, Cyprus, February 2017.

Memberships

  1. Member of the Junior Common Room, Wolfson College, Oxford – February 2016-June 2017.