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    Tissue Engineering

    (I-347) Mechanism of recovery following human stem cell-derived extracellular vesicle treatment to cerebral ischemia

    Thursday, October 12, 2023
    2:00 PM – 3:00 PM PDT
    Location: Exhibit Hall - Row I - Poster # 347

      Presenting Author(s)

    • Yan Li, PhD (she/her/hers)

      Professor
      Florida State University
      Tallahassee, Florida, United States

      • Co-Author(s)

    • SH

      Shannon Helsper

      Graduate Student
      Florida State University, United States

    • LS

      Li Sun

      Research Faculty I
      Florida State University, United States

      • Last Author(s)

    • SG

      Samuel Grant

      Professor
      Florida State University, United States

    Introduction:: Human mesenchymal stem cells (hMSC) have been under investigation in preclinical and clinical settings for the treatment of neurological disorders in recent years. Predominantly due to paracrine effects in vivo, the hMSC secretome consisting of extracellular vesicles (EV) is at the forefront of these investigations. A direct comparison of hMSC and the secreted EV in a preclinical model of ischemic stroke would provide valuable information regarding the mechanisms of recovery that are instituted with a successful therapy onboard.

    Materials and Methods:: In this study, the therapeutic efficacy of hMSC and EV following hypoxia preconditioning were evaluated in a preclinical model of ischemic stroke. The effects of hypoxia on hMSC-EV size, morphology and exosomal markers were evaluated. Cargo analysis using proteomics was performed and compared between culture methods (normoxia vs. hypoxia), in addition to mRNA-seq and proteomics analysis of the parent cells. Magnetic resonance imaging (MRI) following in vivo administration of iron oxide-labeled hMSC and EV provided assessment of biodistribution and therapeutic efficacy.

    Results, Conclusions, and Discussions:: Results: Characterization of hMSC and EV revealed that hypoxia preconditioning upregulated expression of metabolic proteins related to HIF signaling, neurogenesis and EV biogenesis. Tissue recovery assessed via MRI indicated differential recovery in sodium levels in rats following both hMSC and EV administration compared to those who received the vehicle only. Lactate levels and functional recovery support these findings.
    Conclusion: EV derived from hypoxia hMSC localized to the ischemic lesion and evoked a therapeutic response after a single bolus injection. This study has significance in developing human stem cell-derived therapeutics for treating ischemic stroke.

    Acknowledgements (Optional): : This study was supported by NIH R01NS102395 and R01NS125016.

    References (Optional): :