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Multinuclear MRI Reveals Early Efficacy of Stem Cell Therapy in Stroke

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Abstract

Compromised adult human mesenchymal stem cells (hMSC) can impair cell therapy efficacy and further reverse ischemic recovery. However, in vitro assays require extended passage to characterize cells, limiting rapid assessment for therapeutic potency. Multinuclear magnetic resonance imaging and spectroscopy (MRI/S) provides near real-time feedback on disease progression and tissue recovery. Applied to ischemic stroke, 23Na MRI evaluates treatment efficacy within 24 h after middle cerebral artery occlusion, showing recovery of sodium homeostasis and lesion reduction in specimens treated with hMSC while 1H MRS identifies reduction in lactate levels. This combined metric was confirmed by evaluating treatment groups receiving healthy or compromised hMSC versus vehicle (sham saline injection) over 21 days. Behavioral tests to assess functional recovery and cell analysis for immunomodulatory and macrophage activity to detect hMSC potency confirm MR findings. Clinically, these MR metrics may prove critical to early evaluations of therapeutic efficacy and overall stroke recovery.

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Data Availability

All data used in this study were newly acquired. Relevant data used in preparation of this manuscript are available upon request to either the principal or corresponding author via email. In accordance with the National High Magnetic Field Laboratory FAIR Data Management Plan (www.nationalmaglab.org/about/fair-data), data can be made available for access through the NHMFL publication database.

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Funding

This study was funded by National Institutes of Health and the National Institute for Neurological Disorders and Stroke (RO1-NS102395 and F31-NS115409). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A portion of this work was performed at the National High Magnetic Field Laboratory, which is supported by National Science Foundation Cooperative Agreement No. DMR-1644779 and the State of Florida.

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Authors and Affiliations

  1. The National High Magnetic Field Laboratory, Florida State University, 1800 E. Paul Dirac Dr, Tallahassee, FL, 32310, USA

    Shannon Helsper, Xuegang Yuan, F. Andrew Bagdasarian & Samuel C. Grant

  2. Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, 32310, USA

    Shannon Helsper, Xuegang Yuan, F. Andrew Bagdasarian, Jacob Athey, Yan Li & Samuel C. Grant

  3. Center of Excellence for Aging & Brain Repair, University of South Florida, Tampa, FL, 33612, USA

    Cesario V. Borlongan

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  1. Shannon Helsper
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Contributions

S.H. and S.C.G. conceived, designed, and directed the project. S.H. drafted the manuscript, performed all the surgical procedures, and acquired and interpreted all MR data. X.Y. designed and performed all the cell culture and in vitro analysis. J.A. performed and compiled the blind animal behavioral assessments and S.H. interpreted the results. F.A.B. assisted in animal handling and MR acquisition as needed. C.V.B and YL assisted with the interpretation. S.C.G. supervised the project. All the authors contributed to and approved the manuscript.

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Correspondence to Samuel C. Grant.

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All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All animal procedures were completed in accordance with the Animal Care and Use Committee at the Florida State University. All studies were conducted in accordance with the United States Public Health Service's Policy on Humane Care and Use of Laboratory Animals as well as the US NIH Guide for the Care and Use of Laboratory Animals (NIH Publications, No. 8023, 1978 revision).

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Helsper, S., Yuan, X., Bagdasarian, F.A. et al. Multinuclear MRI Reveals Early Efficacy of Stem Cell Therapy in Stroke. Transl. Stroke Res. 14, 545–561 (2023). https://doi.org/10.1007/s12975-022-01057-w

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