Strategies to Enhance Stem Cell Mediated Mitochondrial Disease Transfer

Research Update – April 2014

Mitochondrial diseases are rare, but often devastating conditions with limited treatment options. The varied and often multifaceted nature of mitochondrial diseases requires an approach that will deliver or stimulate the proliferation of healthy mitochondria. A novel approach to accomplish this goal involves the administration of stem cells. Stem cells are early, multi-lineage cells (that can turn into many different cell types) and have immune privilege (not attacked by the immune system). This was the objective of our recent Mito Canada funded project ‘Strategies to enhance stem cell mediated mitochondrial transfer: potential for the treatment of mitochondrial disease’.

In this study, we show stem cells to target sites of mitochondrial dysfunction and to reduce a key hallmark feature associated with the disease, the production of excess reactive oxygen species. This reduction occurred 5 days post-administration, despite the finding that the majority of injected stem cells were no longer present in the liver, the key tissue of interest. This work was recently published. For more information see: Going forward, we are trying to uncover ‘how’ this happens. While the laboratory initially hypothesized direct mitochondrial transfer from stem cells to host tissues, we are now showing stem cells to alter gene expression and mitochondrial networks, resulting in a shift away from mitochondrial metabolism to glycolytic means (from greek “glyco” meaning “sweet” and Greek “lysein” meaning “to break apart”). This shift results in a decreased dependence on mitochondria for energy production and reorganizes mitochondria to favor existing healthy mitochondria. To do this we are collaborating with Dr. Dustin Hittel and the National Children’s Hospital in Washington, DC to examine gene expression profiles of our samples. This will provide insight into how stem cells induce this switch. Data resulting from this study will enhance our understanding of cell-mediated regenerative mechanisms and the eventual development of a novel treatment for mitochondrial disease.

Jane Shearer – April 26, 2014

Grant and Project Information

Date:  May 2013

Award:  $45,000 (one time)

Strategies to Enhance Stem Cell Mediated Mitochondrial Transfer: Potential for the Treatment of Mitochondrial Disease

Jane Shearer, Ph.D.; Jong Rho, MD; Steven Martin, MD; Aneal Khan, MD
Faculty of Kinesiology and Faculty of Medicine,
University of Calgary and Alberta Children’s Hospital

This study examines the utility of cell-based therapy (stem cells) to alleviate symptoms associated with mitochondrial dysfunction.  Stem cells are promising as they are able to reduce oxidative stress, alleviate inflammation and repair damaged tissues. Recent work also shows that they have the ability to transfer healthy mitochondria into host tissues. The goal of this research is to better understand this process and its potential clinical utility for the treatment of mitochondrial disease. The research team is unique as it combines expertise in mitochondrial disease, metabolic physiology, pediatric neurology and cell transplantation. With MitoCanada’s support we envision that our work will one day contribute to a cellular therapy for the treatment of mitochondrial disease.