Organ-on-a-Chip Modeling (PI Plebani)
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Dr. Roberto Plebani's team research focuses on modeling the microphysiology of cystic fibrosis (CF) airways using advanced 3D culture techniques, including organ-on-a-chip technology, with the overall goal of offering new models that will allow to evaluate the efficacy of pharmacological treatment using patient’s derived cells.
The airways of CF patients are characterized by chronic inflammation and persistent infections, accompanied by an exaggerated and pathological migration of neutrophils, exacerbating inflammation and tissue damage. Since such complexities cannot be accurately replicated using traditional 2D cell cultures, Plebani’s interest is particularly focused in 3D culture models for studying the entire inflammatory response: from cytokine production and chemotaxis to leukocyte recruitment and their migration from vessels to the inflamed epithelia.
Dr. Plebani has successfully replicated CF bronchial pathology 'ex vivo' in the first CF airway-on-a-chip composed of a CF pseudostratified human bronchial epithelium and a microvascular endothelium, interacting with neutrophils and bacteria, mimicking mucus accumulation, inflammatory cytokine production, and uncontrolled neutrophil migration. This model, developed in 2021 (Plebani et al., JCF 2021 - DOI: 10.1016/j.jcf.2021.10.004), was achieved in collaboration with the Wyss Institute (Harvard University, Boston, MA, USA).
Overall, the organ-on-a-chip technology has a great advantage: It allows drug testing in a highly reliable microphysiological setting using patients' derived cells, and this implies a high predictive value of the data obtained in 'ex vivo' experiments. On the other hand, patient-derived cells are not easy to obtain, as they are often isolated from organs removed during surgery or post mortem. For this reason, the team is also interested in developing models using cells from more readily available and less invasive sources. These can be respiratory cells obtained from nasal brushing or, even better, reprogrammed stem cells. The latter could represent a breakthrough in the field of organ-on-a-chip technology as well.
Dr. Plebani is currently a key member of the “Organ-on-a-chip” facility at the University of Chieti, Department of Medical, Oral, and Biotechnological Sciences (DSMOB) and CAST. His research is not limited to CF and respiratory diseases, but also extends to the development of other models. Representing one of the leading research groups for this technology in Italy and Europe, the team is open to establishing further collaborations and expanding the facility on behalf of the G. d’Annunzio University, DSMOB, and CAST.
Ongoing and past research projects:
- Grant: Gianni Mastella Starting Grant GMSG#1/2023
Role: Principal Investigator (PI)
Funder: Italian Cystic Fibrosis Foundation (FFC)
Project Title: "Cystic Fibrosis Airway-on-a-Chip 2.0: A New Paradigm for Preclinical Drug Testing and Studies on Inflammation". This project aims to enhance the realism of the "Airway-on-a-chip" model by incorporating fibroblasts and an endogenous stroma. Its ultimate goal is to evaluate the effects of current CF drug treatments on the inflammatory response and bacterial infection.
- Grant: NIH 1R01AI177555- 01
PI: Laurence G Rahme
Role: External collaborator
Project Title: "A comprehensive investigation of Pseudomonas quorum sensing regulatory relationships and the consequences on quorum sensing inhibitors in complex communities."
- EX 60% (2019-20) Released by Università G. d'Annunzio
Role: Project Leader
Project Title: "Study of Pulmonary Microvascular Endothelium in Cystic Fibrosis"
- 60% (2021) Released by Università G. d'Annunzio
Role: Project Leader
Project Title: "Generation of CFTR-Knockout or F508del Mutation-Expressing Clones in 16HBE14o- Bronchial Epithelial Cell Line"
- EX 60% (2022) Released by Università G. d'Annunzio
Role: Project Leader
Project Title: "Utilization of CFTR-Knockout Clones of Bronchial Epithelial Cells for Studying Inflammation in Cystic Fibrosis"
MOST RELEVANT PUBBLICATIONS
- Modeling Pulmonary Cystic Fibrosis in a Human Lung Airway-on-a-chip. Journal of Cystic Fibrosis. 2021. (Plebani R et al., …and Ingber DE).
- A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat Biomed Eng. 2021. (Si L et al., …and Ingber DE) - among authors Plebani R.
- Generation of a live attenuated influenza A vaccine by proteolysis targeting. Nature Biotechnology. 2022. (Si L et al., …and Plebani R).
- Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip. Nature Communications. 2022. (Bai H, et al., …and Ingber DE) - among authors Plebani R.
- Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip. Microbiome 2022. (Mahajan G et al., …and Ingber DE) - among authors Plebani R.
Establishment and long-term culture of human cystic fibrosis endothelial cells. Lab Invest. 2017. (Plebani R et al., …and Romano M).