MEMP PhD Thesis Defense: Alexandra Tchir

Vitrification of isolated mitochondria enables preservation of function and cellular integration

The preservation of mitochondrial integrity and function represents a profound challenge in both foundational and translational research. Beyond its relevance to biological mechanistic studies and the clinical monitoring of mitochondrial disease, the ability to preserve these organelles is critical for the emergence of mitochondrial transplantation as a therapeutic strategy. Artificial mitochondrial transfer has been demonstrated to benefit diverse cell types undergoing injury and has shown promising outcomes in early clinical studies; however, the fragility of isolated mitochondria and their rapid loss of bioenergetic function remain significant bottlenecks. My doctoral work has focused on developing a reproducible platform for mitochondrial isolation and assessment to validate vitrification as a strategy for long-term organelle preservation.

I describe the validation of vitrified mitochondria using cellular and whole-organ models of ischemia as therapeutic testbeds. In in vitro studies using hepatocytes and liver sinusoidal endothelial cells, I report that vitrified mitochondria demonstrate cellular uptake and metabolic efficacy equivalent to fresh controls. Extending this to a clinically relevant ex vivo whole-liver perfusion model, I demonstrate the feasibility of therapeutic delivery, achieving uniform, organ-wide distribution and moderate metabolic support during simulated cold storage injury.

The vitrification strategy I report here enables long-term storage with retention of key functions, including respiration, membrane integrity, and cellular uptake. Beyond basic research applications, these findings provide a foundational step toward the use of cryopreserved mitochondria as an injectable therapeutic for diseases involving mitochondrial dysfunction.

Thesis Supervisors:
Korkut Uygun, Ph.D.
Professor of Surgery, Massachusetts General Hospital and Harvard Medical School

Mehmet Toner, Ph.D.
Helen Andrus Benedict Professor of Surgery, Massachusetts General Hospital and Harvard Medical School

Thesis Committee Chair:
Martha Gray, Ph.D.
Whitaker Professor in Biomedical Engineering 
Professor, Electrical Engineering & Computer Science and Institute for Medical Engineering & Science, Massachusetts Institute of Technology

Thesis Reader:
Heidi Yeh, MD
Surgical Director, Pediatric Transplant, Mass General Brigham for Children

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Topic: Alexandra Tchir MEMP PhD Thesis Defense
Time: Tuesday, December 9, 2025, 3:00 PM Eastern Time (US and Canada)

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