Stem Cells Mediated Mitochondria Transfer and Neuroprotection in Rodent Model of Ischemic Stroke (4083)

Objective: The aim of the study is to understand how intra-arterial (IA) mesenchymal Stem Cells (MSCs) can confer neuroprotection via mitochondria transfer following ischemic stroke in rodents. Background: Stroke is a sudden cerebrovascular event contributing to death and disability in major population worldwide. Mitochondria plays a central role in the various mechanisms that are involved in stroke pathology. For post-ischemic neuroprotection, preserving the mitochondrial functionality is of utmost importance. IA MSCs is promising for stroke therapy with several pre-clinical and clinical studies establishing its safety and efficacy. Transfer of mitochondria from stem cells to damaged cells have been extensively studied in various pathologies and restoration of mitochondrial functionality has been reported following such transfer. Design/Methods: IA MSCs were infused in ovariectomized rats 6 hours post middle cerebral artery occlusion (MCAo) followed by 24 hours of reperfusion. Neurodeficits and motor functioning were evaluated and brains were harvested for infarct estimation, western blot analysis and immunohistochemistry. Brain mitochondria were isolated and analyzed for respiratory capacity, complex assays, membrane potential changes and mitochondrial reactive oxygen species (mitoROS) content. Mitochondria transfer was visualized through microscopy with a possible involvement of SIRT1 in the transfer. Results: Improvements in motor functioning and neurological deficits, with a reduction in infarct size were observed following MSCs infusion. Mitochondrial transfer was observed in the ischemic region. Improvements in mitochondrial respiratory capacity, complex activity and membrane potential were observed. Reduction in mitoROS also occurred. Increased expression of SIRT1, TFAM, MFN1, MFN2, PGC1a, OPA1 and RHOT1 were seen in the cortical brain regions. Conclusions: Mitochondrial transfer from MSCs towards ischemic neurons confer post stroke neuroprotection. Disclosure: Miss Sarmah has nothing to disclose. Aishika Datta has nothing to disclose. Kiran Kalia has nothing to disclose. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson & Johnson. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving as a Consultant for Neural Analytics, Inc. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RAPID MEDICAL LTD. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Neural Analytics, Inc. Dr. Yavagal has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Carnival Cruises. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Royal Carribean Cruises Ltd. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint Global. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Goldberg Segalla LLP. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Rourke and Blumenthal, LLP. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Eadie Hill Trial Lawyers. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Goldberg Segalla LLP. Dr. Bhattacharya has nothing to disclose.