Regenerative Liver Biology and Islet Cell Therapy (Gonelle-Gispert group)


Successful liver regeneration is essential for restoring functional liver mass following surgical resection, transplantation and acute liver injury. Despite the remarkable regenerative capacity of the liver, impaired regeneration remains a major clinical challenge and a leading cause of post-hepatectomy liver failure.

A better understanding of the molecular mechanisms that govern liver regeneration is therefore essential for developing therapies that enhance regenerative capacity and improve patient outcomes.

Liver regeneration and thrombo-inflammation
Beyond their established roles in haemostasis and thrombosis, platelets interact with hepatocytes, endothelial cells, and immune cells during liver injury and regeneration. We hypothesise that coordinated, cell-specific platelet signalling within the hepatic microenvironment shapes regenerative outcomes. Our research aims to define these interactions and identify mechanisms that could be targeted to improve liver regeneration.

Platelet-microenvironment interactions during liver regeneration
We investigate how platelets interact with hepatic macrophages and liver sinusoidal endothelial cells during regeneration. We focus on platelet clearance and macrophage activation, as well as platelet-mediated TGF-β receptor signalling in LSECs and its potential role in vascular and regenerative responses.

Hepatocyte biology and platelet-derived regenerative signalling
We investigate how platelet-derived signals influence hepatocyte re-entry into the cell cycle during the early phases of regeneration. We focus on platelet-derived TGF-β1 and the hypothesis that it helps establish a regeneration-competent hepatocyte state, including the transcriptional and metabolic adaptations required for proliferation.

Porcine islet xenotransplantation and immunomodulation
Achieving local immune tolerance while preserving graft function remains a major challenge for β-cell replacement therapies and the clinical translation of porcine islet xenotransplantation.
We investigate innovative cell-based and immunomodulatory strategies to promote the survival and function of transplanted postnatal porcine islets for the treatment of type 1 diabetes. 
We explore the use of pancreatic-derived mesenchymal stromal cells (MSCs), MSC-derived extracellular vesicles, and immune checkpoint pathways such as PD-L1 to establish a local immune-protective microenvironment that supports long-term graft survival while reducing the need for systemic immunosuppression.

Our multidisciplinary research combines transgenic mouse models, primary human, porcine and murine cell systems, advanced molecular biology and translational studies using human liver tissues. We employ state-of-the-art technologies, including spectral flow cytometry, high-resolution imaging approaches such as confocal and expansion microscopy, transcriptomic and proteomic profiling, and functional analyses of cellular signalling, immune responses and regeneration. Our work integrates fundamental and translational research approaches to uncover mechanisms of liver regeneration and islet graft immunoregulation with strong translational potential to advance regenerative medicine and cell-based therapies.

 

Members

GONELLE-GISPERT Carmen

Senior scientist

Details

FRICK STEFANI Johanna

Scientific Collaborator

Details

Publications

IL-6/GP130/JAK/STAT3 Pathway Activation in Pancreatic Ductal Adenocarcinoma and Its Association With Clinical Features: Protocol for a Retrospective Cross-Sectional Study
Mellenthin, Claudia, Schaller, Fabien, Vignot, Lucie, Peisl, Sarah, Vesce, Rita, Esposito, Irene, Gonelle-Gispert, Carmen, Schneider, Cornelia, Ada-mina, Michel, Buehler, Leo Hans, JMIR Research Protocols (2025) | Journal article

Xenotransplantation: from proof of concept to clinical reality
Hu, Xiaowei, Cooper, David K. C., Golshayan, Dela, Gonelle-Gispert, Carmen, Hirsch, Hans H., Longchamp, Alban, Meier, Raphael P. H., Morel, Philippe, Mueller, Nicolas J., Muller, Yannick D., Pascual, Manuel, Yung, Gisella Puga, Rieben, Robert, Seebach, Jorg D., Buhler, Leo, Schweizerische Medizinische Wochenschrift (2025) | Journal article

Evidence for platelet-derived transforming growth factor β1 as an early inducer of liver regeneration after hepatectomy in mice
Frick, Johanna, Frobert, Aurelien, Pousa, Ana Maria Quintela, Balaphas, Alexandre, Meyer, Jeremy, Schaefer, Katrin, Giraud, Marie-Noelle, Egger, Bernhard, Buhler, Leo, Gonelle-Gispert, Carmen, The FASEB Journal (2024) | Journal article

The international human xenotransplantation inventory: Current data and the need for its integration into a broader registry
Hu, Xiaowei, Geng, Zhen, Gonelle-Gispert, Carmen, Wang, Yi, Hawthorne, Wayne J., Deng, Shaoping, Egger, Bernhard, Buhler, Leo, Transplantation (2024) | Journal article

Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps
Tiantian Lei and Lin Chen and Kejing Wang and Suya Du and Carmen Gonelle-Gispert and Yi Wang and Leo H. Buhler, Frontiers in Immunology (2022) | Journal article

Optimized Isolation and Characterization of C57BL/6 Mouse Hepatic Stellate Cells
Alexandre Balaphas, Jeremy Meyer, Cécile Gameiro, Aurélien Frobert, Marie-Noelle Giraud, Prof. Bernhard Egger, MD, Leo H. Bühler, Cells (2022) | Journal article

Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function
Naomi Koehler and Leo Buhler and Bernhard Egger and Carmen Gonelle-Gispert, Frontiers in Endocrinology (2022) | Journal article

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes
Zhang, Qi, Gonelle-Gispert, Carmen, Li, Yanjiao, Geng, Zhen, Gerber-Lemaire, Sandrine, Wang, Yi, Buhler, Leo, Frontiers in Immunology (2022) | Journal article

Asymmetrical Forces Dictate the Distribution and Morphology of Platelets in Blood Clots
Tatiana A. Kovalenko, Marie-Noelle Giraud, Anita Eckly, Anne-Sophie Ribba, Fabienne Proamer, Sandrine Fraboulet, Nadezhda A. Podoplelova, Jeremy Valentin, Mikhail A. Panteleev, Stéphane Cook, Laurence Lafanechère, Anastasia Sveshnikova, Karin Sadoul, Cells (2021) | Journal article

Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters.
Montanari E and Szabó L and Balaphas A and Meyer J and Perriraz-Mayer N and Pimenta J and Giraud MN and Egger B and Gerber-Lemaire S and Bühler L and Gonelle-Gispert C, Xenotransplantation (2021) | Journal article

Platelets and Platelet-Derived Extracellular Vesicles in Liver Physiology and Disease.
Balaphas A and Meyer J and Sadoul K and Fontana P and Morel P and Gonelle-Gispert C and Bühler LH, Hepatology communications (2019) | Journal article

Systematic review and meta-analysis of thrombocytopenia as a predictor of post-hepatectomy liver failure.
Meyer J and Balaphas A and Combescure C and Morel P and Gonelle-Gispert C and Bühler L, HPB : the official journal of the International Hepato Pancreato Biliary Association (2019) | Journal article