Bridging In Vitro and In Vivo for Mitochondrial Transplantation in Acute Diseases
Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. Current clinical applications focus on the delivery of autologous mitochondria to limit immune responses and rejection.
A Mitochondrial Transplant Convergent Working Group (CWG) was recently convened to explore three key issues limiting clinical translation:
- Storage of mitochondria
- Biomaterials to enhance mitochondrial uptake
- Dynamic models to mimic the recipient tissue environment
Anna C. Andreazza and her team presented a summary of CWG conclusions related to these three issues and provided an overview of pre-clinical studies aimed at building a more robust toolkit for translational trials.
While mitochondrial transplants show promise in animal and early clinical trials, many questions remain. The CWG identified priorities to accelerate progress, including the need for improved storage and delivery of isolated mitochondria, and accurate in vitro models to mimic human tissue complexity.
A research plan was developed to evaluate the stabilization and short-term storage of mitochondria encapsulated in hyaluronic acid, methyl cellulose, and poly(L-lysine). Storing isolated mitochondria enables comprehensive quality control, ensuring healthy and pure transplants, reducing adverse events, and allowing for procedures requiring multiple transplants without repeated isolations.
Organ-on-a-chip models for brain, cardiac, muscle, joint, lung, and liver tissues will be used to evaluate mitochondrial transplants in acute and chronic disease states. This approach allows accurate assessment of clinical applicability and therapeutic mechanisms in vitro, advancing mitochondrial transplant translation across various diseases.
Anna C. Andreazza will be a speaker at the 15th WMS Annual Meeting this October in Berlin. She will discuss advances in mood disorders and mitochondrial-organ transplantation.
Image Credits: Bodenstein, D.F., Siebiger, G., Zhao, Y. et al. Stem Cell Res Ther15, 157 (2024)
