Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states
David F. Bodenstein, Gabriel Siebiger, Yimu Zhao, Aaron J. Clasky, Avinash Naraiah Mukkala, Erika L. Beroncal, Lauren Banh, Lili Aslostovar, Sonya Brijbassi, Sarah Hogan, James D. McCully, Mohadeseh Mehrabian, Thomas Petersen, Lisa A. Robinson, Melanie Walker, Constantine Zachos, Sowmya Viswanathan, Frank Gu, Ori D. Rotstein, Marcelo Cypel, Milica Radisic, Ana C. Andreazza
Abstract
Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment. In this review, we present a summary of CWG conclusions related to these three issues and provide an overview of pre-clinical studies aimed at building a more robust toolkit for translational trials.