Dr Carmine Gentile, PharmD/PhD, FAHA, is a Lecturer within the School of Biomedical Engineering and leads the Cardiovascular Regeneration Group both at UTS and at the Kolling Institute/University of Sydney. He is a Senior Lecturer (Honorary) at the University of Sydney, a Sydney Medical School Foundation Fellow and Visiting Research Fellow at Harvard Medical School.
He received his BSc/MSc (Pharmaceutical Chemistry and Technologies) and PharmD at the University of Pisa, Italy and his PhD in Biomedical Sciences (Cardiovascular) at the Medical University of South Carolina, Charleston, SC, USA, funded by a prestigious American Heart Association Fellowship.
Since 2013 Dr Gentile has worked in Australia at the Heart Research Institute, the University of Sydney and now at UTS, supported by several awards and grants, working within a multidisciplinary team with scientists, industry partners and clinicians to quickly translate his findings from bench to bedside.
Dr Gentile is an internationally recognized expert in the field of 3D bioprinting and stem cell technologies and his more recent studies focus on novel molecular and cellular approaches to treat cardiovascular disease, including myocardial infarction and heart failure. These studies are based on the use of “mini-hearts” he developed as “bioink” for human heart tissues. In 2016, he was invited as Visiting Research Fellow at Harvard Medical School, where he worked towards novel in vitro models using mini-hearts to study human heart physiology. Following his interest for commercialisation pathways for medical devices, Dr Gentile is a Cicada Innovations Graduate (MDCTP, 2018).
His research received media attention and featured on ABC News (2016), ABC Catalyst (2017), Sydney TEDx (2018) and Daily Telegraph (2019).
- 2018 Sydney Medical School (University of Sydney) International Symposium on Experimental & Clinical Cardiovascular Medicine, ECR Travel Support (Sydney, Australia);
- 2017 Heart Research Australia Award for Discovery Biomedical Research (Sydney, Australia);
- 2016 Ian Potter Foundation Award (Melbourne, Australia);
- 2016 AAS Travel Grant to visit Prof Federica del Monte at Harvard Medical School(Australia);
- 2015 Young Investigator Award (Society for Redox Biology and Medicine Meeting, Boston, USA);
- 2015 Charles Perkins Centre Young Achiever Award (Sydney, Australia);
- 2014 Early Career Reasearcher Travel Award (Society for Free Radical Biology and Medicine Annual Meeting, Seattle, USA);
- 2013 First prize for outstanding oral presentation by an early career researcher(Australian Vascular Biology Society Meeting, Barossa Valley, Australia);
- 2013-2016 Marcus Blackmore Postdoctoral Research Fellowship (Heart Research Institute, Sydney, Australia);
- 2011-2013 American Heart Association (AHA) Pre-doctoral Fellowship (USA);
- 2011 American Association of Anatomists (AAA) Student Travel Award (Experimental Biology Meeting, Washington DC, USA);
- 1999-2004 PharmD Fellowship (University of Pisa, Italy).
- American Association of Anatomists (AAA);
- Australian Atherosclerosis Society (AAS);
- American Heart Association (AHA);
- American Physiologist Society (APS);
- Australasian Society for Biomaterials and Tissue Engineering (ASBTE)
- Australian Vascular Biology Society (AVBS);
- Biophysical Society (BPS);
- High Blood Pressure Research Council of Australia (HBPRCA);
- International Society of Heart Research (ISHR)
- Society for Free Radical Biology and Medicine (SFRBM);
- Tissue Engineering and Regenerative Medicine International Society (TERMIS).
- American Heart Association – Predoctoral Fellowship (11PRE7530048, Role on project: Principal Investigator). Project Title: VEGF/Akt-mediated Endothelial Nitric Oxide Synthase Phosphorylation as a Regulator of Endothelial Cell Division. 01/07/11–30/06/13
- Heart Research Institute – Marcus Blackmores Fellowship (Role on Project: Principal Investigator). Project title: VEGF/eNOS signaling regulates the differentiation from Adipose Derived Stem Cells (ADSCs) into Cardiomyocytes (CMs) 01/03/13–31/12/16
- The Bosch Institute – University of Sydney – Translational Grant-In-Aid (Role on Project: Co-Investigator) Project Title: Human Cardiac Tissue Spheroids (HCTSs): A Cardiotoxicity Assay 01/10/13–30/09/14
- Ian Potter Foundation (Role on Project: Principal Investigator) Project Title: Bioprinting of Human Cardiac Patches for Heart Regeneration using Spheroids from Human Pluripotent Stem Cells. 01/06/16–31/05/19
- University of Sydney – Kickstart Grant (Role on Project: Principal Investigator) Project Title: Bioprinted cardiac spheroids as novel models of the human heart. 01/01/17–12/01/18
- National Health and Medical Research Council (APP1129685, Role on Project: Chief Investigator F) Project Title: A new paradigm in redox-mediated cardiac fibrosis 01/01/17–31/12/20
- University of Sydney/Sydney Medical School Foundation/Cardiothoracic Surgery Research Grant Scheme (Role on Project:Principal Investigator) Project Title: Bioprinting human cardiac patches for heart regeneration 01/07/17–30/01/2021
- University of Sydney/DVC Research/Community & Industry Engagement Fund (Role on Project: Principal Investigator) Project Title: CDIP Industry & Community Engagement Fund 2017: 3D bioprinting of the human heart using patient-derived cells 01/12/17–31/12/18
- University of Sydney/Sydney Medical School/Industry Engagement Seed Fund (Role on Project: Principal Investigator) Project Title: 3D bioprinting of novel in vitro patient-specific human heart models for drug discovery and cardiotoxicity 01/12/17-30/11/19
- University of Technology Sydney/FEIT Cross Faculty Collaboration Scheme (Role on Project: Co-Investigator) Project Title: Three dimensional bio-printing – establishing the future of personalised medicine approaches for women's cancers at UTS 01/07/19–30/06/20
Can supervise: YES
- 3D Bioprinting of Vascularized Organs and Tissues
- Stem Cells
- Personalised approaches for Tissue Engineering and Regenerative Medicine
- 3D bioprinted in vitro disease models
- 3D bioprinted in vitro models of cardiotoxicity and drug testing
- Cardiovascular Biology, Pathology and Pharmacology
- 42026 – Biomedical Polymers (2020)
Gentile, C, Kesteven, S, Wu, J, Davies, MJ, Bursill, C, Feneley, M & Figtree, G 2020, 'Endothelial nitric oxide synthase plays a protective role in endothelial cells and cardiomyocytes against myocardial infarction', Journal of Molecular and Cellular Cardiology, vol. 140, pp. 31-31.View/Download from: Publisher's site
Roche, CD, Brereton, RJL, Ashton, AW, Jackson, C & Gentile, C 2020, 'Current challenges in three-dimensional bioprinting heart tissues for cardiac surgery.', European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.View/Download from: Publisher's site
Previous attempts in cardiac bioengineering have failed to provide tissues for cardiac regeneration. Recent advances in 3-dimensional bioprinting technology using prevascularized myocardial microtissues as 'bioink' have provided a promising way forward. This review guides the reader to understand why myocardial tissue engineering is difficult to achieve and how revascularization and contractile function could be restored in 3-dimensional bioprinted heart tissue using patient-derived stem cells.
Gentile, C, Kesteven, S, Wu, J, Bursill, C, Davies, MJ & Figtree, G 2019, 'Abstract 138: A Novel Cellular and Genetic Approach to Investigate the Cardioprotective Role Played by Endothelial Nitric Oxide Synthase in Myocardial Infarction', Circulation Research, vol. 125, no. Suppl_1.View/Download from: Publisher's site
Gentile, C, Kesteven, S, Wu, J, Bursill, C, Davies, M, Feneley, M & Figtree, G 2018, 'Endothelial nitric oxide synthase plays a protective role against myocardial infarction', FREE RADICAL BIOLOGY AND MEDICINE, vol. 128, pp. S26-S26.View/Download from: Publisher's site
Aryal, M, Fischer, K, Gentile, C, Gitto, S, Zhang, YZ & McDannold, N 2017, 'Effects on P-glycoprotein expression after blood-brain barrier disruption using focused ultrasound and microbubbles', PLoS ONE, vol. 12, no. 1.View/Download from: Publisher's site
© 2017 Aryal et al. Many blood-borne substances attempting to pass through the luminal membrane of brain endothelial cells are acted upon by a variety of metabolizing enzymes or are actively expelled back into the capillary lumen by embedded efflux transporters, such as Permeability-glycoprotein (Pgp). Overexpression of this protein has also been linked to multidrug resistance in cancer cells. Previous studies have shown that focused ultrasound (FUS), when combined with a microbubble agent, has ability to temporarily disrupt blood-brain barrier (BBBD). In this work, we investigated whether modulation of Pgp expression is part of the FUS-induced effects. We found that ultrasound can temporarily suppress Pgp expression. When BBBD was produced at 0.55 MPa, Pgp was suppressed up to 48 hours and restored by 72 hours. At 0.81 MPa, suppression can last 72 hours or longer. These findings support the idea that microbubble-enhanced FUS disrupts the functional components of the BBB through suppression of drug efflux.
Figtree, GA, Bubb, KJ, Tang, O, Kizana, E & Gentile, C 2017, 'Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis', CELLS TISSUES ORGANS, vol. 204, no. 3-4, pp. 191-198.View/Download from: Publisher's site
Jiang, L, Gentile, C, Lauto, A, Cui, C, Song, Y, Romeo, T, Silva, SM, Tang, O, Sharma, P, Figtree, G, Gooding, JJ & Mawad, D 2017, 'Versatile Fabrication Approach of Conductive Hydrogels via Copolymerization with Vinyl Monomers', ACS APPLIED MATERIALS & INTERFACES, vol. 9, no. 50, pp. 44124-44133.View/Download from: Publisher's site
Polonchuk, L, Chabria, M, Badi, L, Hoflack, J-C, Figtree, G, Davies, MJ & Gentile, C 2017, 'Cardiac spheroids as promising in vitro models to study the human heart microenvironment', SCIENTIFIC REPORTS, vol. 7.View/Download from: Publisher's site
Gentile, C 2016, 'Filling the Gaps between the In Vivo and In Vitro Microenvironment: Engineering of Spheroids for Stem Cell Technology', CURRENT STEM CELL RESEARCH & THERAPY, vol. 11, no. 8, pp. 652-665.View/Download from: Publisher's site
Polonchuk, L, Chabria, M, Davies, MJ & Gentile, C 2016, 'Doxorubicin-Mediated Toxic Effects Are Mediated Via NO/eNOS in a Novel 3D in Vitro Model of the Human Heart', FREE RADICAL BIOLOGY AND MEDICINE, vol. 100, pp. S142-S142.View/Download from: Publisher's site
Galougahi, KK, Liu, C-C, Garcia, A, Gentile, C, Fry, NA, Hamilton, EJ, Hawkins, CL & Figtree, GA 2016, 'beta 3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia', JOURNAL OF THE AMERICAN HEART ASSOCIATION, vol. 5, no. 2.View/Download from: Publisher's site
Di Bartolo, BA, Cartland, SP, Prado-Lourenco, L, Griffith, TS, Gentile, C, Ravindran, J, Azahri, NSM, Thai, T, Yeung, AWS, Thomas, SR & Kavurma, MM 2015, 'Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Promotes Angiogenesis and Ischemia-Induced Neovascularization Via NADPH Oxidase 4 (NOX4) and Nitric Oxide-Dependent Mechanisms', JOURNAL OF THE AMERICAN HEART ASSOCIATION, vol. 4, no. 11.View/Download from: Publisher's site
Gentile, C, Drake, CJ, Figtree, G & Davies, MJ 2014, 'Post-Transcriptional Regulation of eNOS and S-Nitrosylation of Cell Cycle-Related Proteins in Human Endothelial Cells', FREE RADICAL BIOLOGY AND MEDICINE, vol. 76, pp. S43-S44.View/Download from: Publisher's site
Galougahi, KK, Liu, C-C, Gentile, C, Kok, C, Nunez, A, Garcia, A, Fry, NAS, Davies, MJ, Hawkins, CL, Rasmussen, HH & Figtree, GA 2014, 'Glutathionylation Mediates Angiotensin II-Induced eNOS Uncoupling, Amplifying NADPH Oxidase-Dependent Endothelial Dysfunction', JOURNAL OF THE AMERICAN HEART ASSOCIATION, vol. 3, no. 2.View/Download from: Publisher's site
Gentile, C, Muise-Helmericks, RC & Drake, CJ 2013, 'VEGF-mediated phosphorylation of eNOS regulates angioblast and embryonic endothelial cell proliferation', DEVELOPMENTAL BIOLOGY, vol. 373, no. 1, pp. 163-175.View/Download from: Publisher's site
Fleming, PA, Argraves, WS, Gentile, C, Neagu, A, Forgacs, G & Drake, CJ 2010, 'Fusion of uniluminal vascular spheroids: A model for assembly of blood vessels', Developmental Dynamics, vol. 239, no. 4, pp. spcone-spcone.View/Download from: Publisher's site
Fleming, PA, Argraves, WS, Gentile, C, Neagu, A, Forgacs, G & Drake, CJ 2010, 'Fusion of Uniluminal Vascular Spheroids: A Model for Assembly of Blood Vessels', DEVELOPMENTAL DYNAMICS, vol. 239, no. 2, pp. 398-406.View/Download from: Publisher's site
Visconti, RP, Kasyanov, V, Gentile, C, Zhang, J, Markwald, RR & Mironov, V 2010, 'Towards organ printing: engineering an intra-organ branched vascular tree', EXPERT OPINION ON BIOLOGICAL THERAPY, vol. 10, no. 3, pp. 409-420.View/Download from: Publisher's site
Mironov, V, Zhang, J, Gentile, C, Brakke, K, Trusk, T, Jakab, K, Forgacs, G, Kasyanov, V, Visconti, RP & Markwald, RR 2009, 'Designer 'blueprint' for vascular trees: Morphology evolution of vascular tissue constructs', Virtual and Physical Prototyping, vol. 4, no. 2, pp. 63-74.View/Download from: Publisher's site
Organ printing is a variant of the biomedical application of rapid prototyping technology or layer-by-layer additive biofabrication of 3D tissue and organ constructs using self-assembled tissue spheroids as building blocks. Bioengineering of perfusable intraorgan branched vascular trees incorporated into 3D tissue constructs is essential for the survival of bioprinted thick 3D tissues and organs. In order to design the optimal 'blueprint' for digital bioprinting of intraorgan branched vascular trees, the coefficients of tissue retraction associated with post-printing vascular tissue spheroid fusion and remodelling must be determined and incorporated into the original CAD. Using living tissue spheroids assembled into ring-like and tube-like vascular tissue constructs, the coefficient of tissue retraction has been experimentally evaluated. It has been shown that the internal diameter of ring-like and the height of tubular-like tissue constructs are significantly reduced during tissue spheroid fusion. During the tissue fusion process, the individual tissue spheroids also change their shape from ball-like to a conus-like form. A simple formula for the calculation of the necessary number of tissue spheroids for biofabrication of ring-like structures of desirable diameter has been deduced. These data provide sufficient information to design optimal CAD for bioprinted branched vascular trees of desirable final geometry and size.
Gentile, C, Fleming, PA, Mironov, V, Argraves, KM, Argraves, WS & Drake, CJ 2008, 'VEGF-mediated fusion in the generation of uniluminal vascular spheroids', Developmental Dynamics, vol. 237, no. 12, pp. spc1-spc1.View/Download from: Publisher's site
Gentile, C, Fleming, PA, Mironov, V, Argraves, KM, Argraves, WS & Drake, CJ 2008, 'VEGF-Mediated Fusion in the Generation of Uniluminal Vascular Spheroids', DEVELOPMENTAL DYNAMICS, vol. 237, no. 10, pp. 2918-2925.View/Download from: Publisher's site
Campbell, M, Chabria, M, Figtree, GA, Polonchuk, L & Gentile, C 2019, 'Stem Cell-Derived Cardiac Spheroids as 3D In Vitro Models of the Human Heart Microenvironment.' in Stem Cell Niche, Springer, Switzerland, pp. 51-59.View/Download from: Publisher's site
Our laboratory has recently developed a novel three-dimensional in vitro model of the human heart, which we call the vascularized cardiac spheroid (VCS). These better recapitulate the human heart's cellular and extracellular microenvironment compared to the existing in vitro models. To achieve this, human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes, cardiac fibroblasts, and human coronary artery endothelial cells are co-cultured in hanging drop culture in ratios similar to those found in the human heart in vivo. The resulting three-dimensional cellular organization, extracellular matrix, and microvascular network formation throughout the VCS has been shown to mimic the one present in the human heart tissue. Therefore, VCSs offer a promising platform to study cardiac physiology, disease, and pharmacology, as well as bioengineering constructs to regenerate heart tissue.
Campbell, M, Surija, L, Peceros, K, Sharma, P, Figtree, G & Gentile, C 2019, 'Stem cell spheroids' in Encyclopedia of Tissue Engineering and Regenerative Medicine, pp. 387-393.View/Download from: Publisher's site
© 2019 Elsevier Inc. All rights reserved. Stem cells are undifferentiated cells that reside in a dynamic, specialized microenvironment (or niche) and play a fundamental role in embryogenesis, tissue homeostasis and regeneration. Three-dimensional stem cell spheroid cultures have emerged as a promising alternative to culture, maintain and differentiate stem cells in vitro by better mimicing the in vivo stem cell niche. These spheroid cultures recapitulate cellular and extracellular features of the in vivo stem cell niche, including biochemical and biophysical cues, which regulate stem cell self-renewal and differentiation potential. This review will provide an overview of the essential features of the niche typical of different stem cell types, to better engineer in vitro culture systems for enhanced stem viability and better control over stem cell behavior and fate. Finally, this review will delve into the many exciting applications of stem cell spheroid culture, including in vitro models of human disease, high-throughput drug discovery and toxicity assays, as well stem-cell based regenerative therapies and 3D bioprinting of organs for transplantation.
© Springer Nature Singapore Pte Ltd. 2019. Cardiovascular disease (CVD) is a major public health problem, particularly in the industrialised world, with diverse causes. Central to these underlying aetiologies is a progressive loss of functional cardiomyocytes, maladaptive remodelling, and resultant cardiac dysfunction. The ageing heart is characterised by perturbations in numerous signalling pathways, impairing its ability to repair and replace injured cardiomyocytes. This is caused at least in part by dysregulation of redox signalling- both in regard to production of reactive oxygen species (ROS), and disruption of cellular protective mechanisms. Cardiac regeneration is one area of particular therapeutic promise, which seeks to ameliorate cardiac function by either (1) direct application of stem cells, (2) modification of molecular signalling pathways to restore the endogenous reparative capacity of the heart, or (3) a combination of these two approaches. Unravelling these molecular and cellular signalling pathways is paramount to unlocking the potential of cardiac regenerative therapies, and theoretically revolutionising the medical management of patients with heart failure. In this chapter, we will review the role of oxidative stress in cardiovascular disease, and the pathophysiological molecular signalling pathways that are involved in the transition from young to ageing heart. We will then provide an overview of the molecular therapies that are used to target these pathways to enhance heart regeneration, future directions involving cellular and novel 'bio-printing' based approaches, in addition to current promising clinical trials.
Gentile, C, Kuehn, B, Davies, MJ & dos Remedios, CG 2014, 'A Novel Method for Isolating and Culturing Human Cardiomyocytes from Cryopreserved Tissues', BIOPHYSICAL JOURNAL, 58th Annual Meeting of the Biophysical-Society, CELL PRESS, San Francisco, CA, pp. 564A-564A.View/Download from: Publisher's site
- Inventia Life Sciences (Australia) – Dr Cameron Ferris
- REGEMAT3D (Spain) – Dr José Manuel Baena
- Medical University of South Carolina/Harvard Medical School (USA) – Prof Federica del Monte
- University of New South Wales (Australia) – Dr Damia Mawad
- Victor Chang Cardiac Research Centre (Australia) – Prof Michael Feneley
- Baker IDI (Australia) – Prof Rebecca Ritchie
- University of Copenhagen (Denmark) – Prof Michael J Davies
- "E. Piaggio" Bioengineering Centre/University of Pisa, Pisa, (Italy) – Prof Giovanni Vozzi
- 3D Solutions (Russia) – Prof Vladimir Mironov
- National Research Council – Institute on Membrane Technology ITM-CNR (Italy) – Dr Loredana de Bartolo