Induced Pluripotent Stem Cells . 3D Engineered Myocardium . Regeneration . In Vitro Disease Modelling . Angiogenesis . Small Diameter Vascular Grafts .
Cardiac Surgery and Engineering
Engineered models mimicking inherited and acquired cardiac diseases in vitro and therapeutic strategies for cardiac repair and regeneration
Our research group advances state-of-the-art iPSC-based myocardial tissue engineering through expertise in therapeutic angiogenesis, scalable production of cardiac cell populations, and sophisticated 3D tissue culture technologies. The platform leverages large-scale differentiation of ventricular cardiomyocytes from human iPSCs, generating highly pure populations for subsequent applications. By application of external biophysical cues and supporting cell types, such as cells from the stromal vascular fraction (SVF), we strive to support / establish organotypic cellular organization into bioartificial myocardium. These engineered tissues have diverse and purpose-dependent geometries, ranging from miniaturized splints to large 3D patches (Kensah 2011; Kensah 2013; Reid, 2025; Borisov, 2023).
The primary focus of our research is the development of engineered cardiac tissues with high resemblance to native myocardium for disease modeling and with high angiogenic and reparative potential for regenerative applications.
Advanced perfusion-based bioreactor systems and biomimetic stimulations enable high-fidelity recapitulation of the myocardial microenvironment, promoting cardiomyocyte maturation, contractility, and survival. Mechanical, electrical and perfusion cues effectively mimic physiological and pathophysiological cardiac conditions and capillary flow (Pisanu, 2022, Sileo and Gabetti, 2025).
These engineered constructs are employed to investigate physiological and pathological cardiac mechanisms, enabling detailed phenotyping of congenital and acquired cardiomyopathies. These include early-onset hypertrophic cardiomyopathy, cardiac ischemia and fibrosis, and to model pathological tissue responses such as post-ischemic scar formation (Mainardi, 2022, Zimmermann 2026). For congenital conditions, such as Noonan syndrome-associated hypertrophic cardiomyopathies, we apply gene-editing technologies, including CRISPR-Cas systems to generate disease models to elucidate unknown pathomechanisms and disease progression and to test novel therapeutic interventions (Nakhaei-Rad et al., 2023). Biosensor-enabled and optogenetic iPSC lines further allow real-time, non-invasive functional assessment and targeted activation within organoid and tissue platforms.
With a focus on regeneration, we develop engineered tissue patches from SVF and parenchymal cells, optimizing paracrine-mediated and intercellular interaction-based mechanisms for regenerating and rescuing ischemic and hibernating myocardium, respectively. We recently showed that perfusion-cultured SVF patches displayed enhanced in vivo vascularization and cell engraftment in preclinical in vitro models (Reid, 2025; Borisov, 2023). Our integrated multimodal medium-throughput bioreactor infrastructure platforms allow systematic exploration of combinatorial stimulations, deep-phenotyping, disease modeling, and candidate treatment evaluation under precisely controlled conditions (Kensah 2011, Pisanu 2022, Patent No.: US 2022/0411734 A1, EP3831925A1; EP19165964, DE102024127433A1).
By combining stem cell engineering, vascular biology, biomaterials, and biophysical conditioning, we strive to address key translational challenges in myocardial regeneration. Our approach leverages mature, vascularized, and highly functional heart muscle tissues to develop advanced in vitro models and therapies for inherited and ischemic heart diseases.
Our research is funded by the Swiss National Science Foundation, Swiss Heart Foundation, Swiss Nanoscience Institute, the University Hospital of Basel (USB), and the University of Basel (Unibas).
References to be finalized:
1. Fawad J, …, Kutschka I, …, Baraki H, …, Kensah G, ..., Zimmermann WH. Engineered heart muscle allografts for heart repair in primates and humans. Nature, 2025
2. Reid G, Cerino G, Melly L, Fusco D, Zhang C, Reuthebuch O, Milan G. Marsano A. Harnessing the angiogenic potential of adipose-derived stromal vascular fraction cells with perfusion cell seeding. Stem Cell Res Ther, 2025.
3. Borisov V, Gili Sole L, Reid G, Milan G, Hutter G, Grapow M, Eckstein FS, Isu G, Marsano A. Upscaled Skeletal Muscle Engineered Tissue with In Vivo Vascularization and Innervation Potential, Bioengineering (Basel). 2023.
4. Nakhaei-Rad S, …, Kensah G, Ahmadian R. Molecular and cellular evidence for the impact of a hypertrophic cardiomyopathy-associated RAF1 variant on the structure and function of contractile machinery in bioartificial cardiac tissues, Biol Communications, 2023
5. Sileo A, Gabetti S, Gülan AC, Cervenka I, Zhang C, Mingels A, Milan G, Massai D, Marsano A. Asymmetric biphasic electric stimulation supports cardiac maturation and functionality. J Tissue Eng. 2025 Nov 28;16:20417314251393556. doi: 10.1177/20417314251393556.
6. Pisanu A. Reid G, Fusco D, Sileo A, Robles Diaz D, Tahrini H., Putame G. Massai D, Isu G, Marsano A. Bi-zonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor, iScience, 2022.
7. Mainardi A, Carminati F, Ugolini GS, Occhetta P, Isu G, Robles Diaz D, Reid G, Visone R, RasponiM, Marsano A. A dynamic microscale mid-throughput fibrosis model to investigate the effects of cardiomyocytes on fibroblast activation. Lab on a Chip, 2021.
8. Zimmermann T, Koechlin L, Walter J, …, Marsano A*, Hammarsten O*, Mueller C*. The cTnI/cTnT Ratio in Myocardial Injury: A Multicohort and Experimental Synthesis. IT-Ratio Consortium. J Am Coll Cardiol. 2026 Feb 17:S0735-1097(25)10659-1. doi: 10.1016/j.jacc.2025.12.078. Online ahead of print.
9. Kensah G, …, Martin U. Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro, European Heart Journal, 2013
10. Kensah G, …, Martin U. A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation, Tissue Engineering Part C, 2011
