MSC-donated mitochondria increase functional viability of islet beta cell transplantation for treating diabetes

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Allogenic transplantation of insulin-secreting islet β-cells offers the possibility of treating type 1 diabetes (T1D); however, the stress islets undergo during preparation for transplantation compromises their functional viability and poses a major obstacle to their adoption as a treatment for the majority of patients. A study released today in STEM CELLS offers information to help overcome this drawback.

Human Mesenchymal Stromal Cells transfer mitochondria to neighboring human islet beta cells in direct contact co-culture.

Allogenic transplantation of insulin-secreting islet β-cells offers the possibility of treating type 1 diabetes (T1D); however, the stress islets undergo during preparation for transplantation compromises their functional viability and poses a major obstacle to their adoption as a treatment for the majority of patients. A study released today in STEM CELLS offers information to help overcome this drawback.

Previous studies have shown that mouse mesenchymal stem cells (MSCs) can boost donor islet β-cells’ survival and function during the co-culturing process prior to transplantation. But the STEM CELLS study is the first to show that mitochondria – the organelles that power a cell — are what is behind the improvement.

“When mitochondria are impaired, islet β-cells can’t produce insulin effectively, and they also tend to die off. In our study, we addressed the hypothesis that the MSCs act as mitochondrial donors during the co-culturing process, transferring functional mitochondria directly to adjacent islets,” said Chloe Rackham, Ph.D., of the Department of Diabetes, Faculty of Life Sciences and Medicine, King’s College London, and lead investigator of the SC study.

Their hypothesis appears to be spot on. The study results showed that MSCs transfer mitochondria to islet β-cells during in vitro co-culture, a process that occurs at least partially through tunneling nanotube-like structures. This transfer correlated with an increase in islet mitochondrial oxygen consumption and enhanced glucose-induced insulin secretion.

“Other interesting results from the study show that mitochondrial transfer from human MSCs to human islets is more extensive than from mouse MSCs to mouse islets, most likely because isolated human islets are exposed to more extreme cellular stressors which initiate mitochondria transfer to human islets,” Dr. Rackham said.

These findings suggest that the mitochondrial donation capacity of MSCs should be harnessed to ensure the functional longevity of transplanted human islets in clinical protocols, she and her team concluded.

“The capability of mesenchymal stromal cells to transfer mitochondria into other cellular targets is highly interesting,” said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. “This is an important new report indicating a potential future therapeutic benefit to that biological phenomenon.”

The full article, “Optimizing beta cell function through mesenchymal stromal cell mediated mitochondria transfer,” can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3134.

Full caption for figure: Human Mesenchymal Stromal Cells transfer mitochondria to neighboring human islet beta cells in direct contact co-culture. Ensuring optimal beta cell mitochondrial mass and bioenergetics through MSC-mediated mitochondria transfer offers a novel strategy for improving the outcomes of clinical islet transplantation as a therapy for Type 1 Diabetes.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

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Chelsea Kekahuna
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