EXCELERATE – Advancing the manufacturing of EXtracellular vesicles derived from human pluripotent stem CELls for cardiac rEgeneRATive medicine

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Designação do Projeto | Project Name EXCELERATE –  Advancing the manufacturing of EXtracellular vesicles derived from human pluripotent stem CELls for cardiac rEgeneRATive medicine

Código do Projeto | Project Code 2022.10467.PTDC

Domínio Científico | Scientific Domain Chemical Engineering

Entidade beneficiária | Beneficiary Entity iBET – Instituto de Biologia Experimental e Tecnológica

Data de início | Starting Date 01/01/2023

Data de conclusão | Conclusion Date 31/12/2025

Breve Descrição do Projeto | Brief Project Description

In cardiac regenerative medicine, there is a rising interest in using extracellular vesicles (EV) as cell-mimetic therapeutics, not only due to their expected superiority, but also because of their advantages over cell transplantation, such as absence of oncologic risk and low immunogenicity. Several studies have focused on the cardioprotective and angiogenic potential of EVs derived mainly from mesenchymal stem cells and cardiac progenitors, and more recently, from human induced pluripotent stem cells (hiPSC) and cardiac derivatives.

However, the translation of EVs as a standalone therapeutic concept into the medical practice will depend on their ability to be manufactured in a clinically relevant scale, under cGMP-compatible conditions.

Recent studies from iBET’s Stem and Immune Cells Bioengineering Lab have shown that the functional benefits of EVs isolated from hiPSC and derived cardiomyocytes (hiPSC-CM) depend on the cell differentiation state. This highlights the need of standardizing methods to manufacture well-characterized and potent cell-derived EV.

To address this, the EXCELERATE project aims to implement reproducible EV production as well as EV isolation methods from conditioned media, collected at specific stages of the hiPSC differentiation and maturation process. The team has extensive knowledge on hiPSC bioprocessing using 3D culture and environmentally controlled stirred-tank bioreactors to develop robust strategies for hiPSC expansion and differentiation/maturation into the cardiac lineage. They have also successfully implemented advanced in vitro 3D model of myocardial ischemia/reperfusion injury, in which we started to shed light into the paracrine mechanisms upregulated in cardiomyocytes following an acute MI. The project will leverage on these abilities to provide a basis for excelling EV research into clinical application.

The ultimate goal of EXCELERATE project is to streamline the manufacturing of therapeutic EV, by integrating basic science and engineering knowledge on hiPSC/EV biology, biological engineering and bioprocessing to “excelerate” EV translation into clinical application. It aims to obtain a potent EV-based product, manufactured under scalable and cGMP-compatible conditions and thoroughly characterized by a robust analytical toolbox.