Advancements in Animal-Free Research and Translational Medicine

Clinical Potential of MSC-EVs and Translational Challenges

Prof. Dr. rer. nat. Bernd Giebel

Human mesenchymal stromal cells (MSCs) are a therapeutically relevant, heterogeneous cell entity with immunomodulatory and pro-regenerative potentials. MSCs mediate a huge proportion of their therapeutic effects via extracellular vesicles (EVs). Connected to several advantages in using cell-free products for the therapeutic setting, MSC-EVs emerged as promising novel therapeutic agents for various diseases, including graft-versus-host disease (GvHD), ischemic stroke, COVID-19 and sepsis.

It is our current mission to optimize the MSC-EV production strategy in a scaled, GMP-compliant manner, and to set up an appropriate quality control platform to translate MSC-EVs into the clinics. One of the challenging aspects in this context is inherited from the MSC field, i.e. contradictory reports on the efficacy of MSC therapies. Not all MSC products mediate therapeutic effects when applied to patients. Similarly, we observe functional differences among independent MSC-EV preparations; even when the same MSC stocks were used as starting material. Thus, to avoid drawbacks as they occurred in the MSC field by failing to show efficacy in a phase III clinical trial for GvHD treatment, it is one of our most important missions to address and appropriately handle the heterogeneity aspect. To this end, we have set up a lentiviral, hTERT-based immortalization strategy and raised MSC lines at the clonal level. EVs released by these clonally expanded immortalized MSCs (ciMSCs) reveal immunomodulatory activities and confer therapeutic activities in vivo. According to our understanding, we thus have fulfilled an essential milestone towards scaled and standardized production of MSC-EV-based therapeutics.

Cardiac organoids: Scaling up for preclinical studies

PD Dr. Kurt Pfannkuche

Cardiac organoids (COs) derived from human induced pluripotent stem (iPS) cells contain the major cell types of the heart. COs are therefore promising for transplantation in experiments to restore infarcted heart tissue. Today, iPS cell technologies are moving from basic research to (pre-)clinical applications. Therefore, protocols need to be adapted to be compatible with GMP manufacturing to streamline the clinical translation of research results. In this presentation, a technology to generate COs in stirred bioreactors under defined FCS-free conditions will be presented and new developments in bioreactor technologies will be discussed.

Humanized Multi-Organoid Disease Models

Dr. Raquel Sousa

Advancing 3D drug development models from the in vitro to the ex vivo level

Conventional cellular or animal disease models have shown that the predictability of patient response to treatment with those models is severely limited. Great efforts have been made to humanize mouse models to better predict certain aspects of human physiology and immunology but with limited success. The abc biopply team has now made a significant breakthrough in humanizing upstream 3D cell models through the revolutionary and proprietary 3D CoSeedis multi-organoid in-chip communication technology™. Providing optimized physiological growth conditions and unique ways of intercellular communication, our models are freed from non-human components. Thus, they allow us to mimic and maintain physiologically relevant organoids in culture under reproducible and reliable conditions. Combined with the unique and statistically powerful predictiveness of the 3D CoSeedis™ chip, we are finally in a position to successfully bridge the translational gap between preclinical predictions and clinical treatments. Here we present how the innovative 3D CoSeedis in chip communication technology™ enables the humanization of 3D multi-organoid models and consequently improves the predictability of patient response. Preliminary data also suggests that the model is even capable of making accurate predictions on gender-specific drug responses.