Improving ex vivo lung perfusion with negative pressure ventilation and mobilization

The objectives of DC2 are to:

1. Assess the performances of a new EVLP device (named “Revolution”) in a pig model. This system enables lung rehabilitation using  negative pressure ventilation - closer to physiology-  and continuous lung mobilization to prevent edema

2. Compare the transcriptomic profiles (bulk RNA-seq, single cell RNA-seq) between the classical EVLP (positive pressure ventilation) and the Revolution device (negative pressure ventilation)

3. Evaluate the Revolution device on human lungs for translational perspectives

4. Evaluate the capacity of the Revolution device in EVLP procedures of prolonged duration (> 12 hours EVLP). 

The project aims to achieve the following outcomes: 1. Preclinical demonstration of the advantages of negative pressure ventilation in promoting lung recovery. This includes improved gas exchange (high oxygenation), enhanced lung compliance, minimal edema formation, and a reduced inflammatory response, validated in both porcine and human ex vivo models. 2. Mechanistic insights into the lung's response to negative versus positive pressure ventilation, through transcriptomic analysis (bulk and single-cell RNA-seq), identifying cell-type–specific and gene-level differences. 3. Groundwork for clinical translation, including defining the key steps toward clinical implementation and outlining a pathway for potential commercialization of the Revolution device.

The candidate will benefit from a transdisciplinary supervision, by a thoracic surgeon and an immunologist, ensuring both clinical and mechanistic insights into the project. Technical training will be provided by an experienced engineer skilled in a wide range of laboratory techniques. Additionally, the candidate will collaborate closely with a bioinformatician for data analysis.

The Hôpital Foch group has already generated promising preliminary results with   Revolution, demonstrating the device’s potential to yield meaningful biological results. The candidate’s contributions will be key to building upon this foundation, driving the research toward high-impact publications and laying the groundwork for clinical translation and commercialization.

Enrolment in Doctoral School: Signaling and Integrated Networks in Biology (BIOSIGNE) https://www.universite-paris-saclay.fr/en/doctoral-schools/signaling-and-integrated-networks-biology.

Planned secondments:

• Lund University, Sweden: Evaluation of neutrophil extracellular  formation upon positive and negative pressure ventilation (months 10-15)

• XVIVO Perfusion AB: learning to use the medical device XPS. Acquiring foundational knowledge for the commercial dissemination of an innovation (months 34-36)