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Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1 T

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Abstract

Extended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by 1H and 23Na magnetic resonance imaging (MRI) at 21.1 T to investigate cellular localization, migration, and recovery over an extended timeframe. MRI provides quantifiable metrics of tissue status through sodium distributions in addition to traditional proton imaging. Quantitative 23Na MRI revealed a significant decrease of sodium concentrations following hMSC aggregate implantation, indicating recovery of homeostasis. This result correlates positively with extended neurological recovery assessed by behavioral analysis and immunohistochemistry. These findings demonstrate the potential of implanted hMSC aggregate therapy to provide extended treatment for ischemic stroke, as well as the robustness of MRI for monitoring such approaches. This method potentially can be translated to a clinical setting for the assessment of extended cell therapy efficacy.

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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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Acknowledgements

This paper is dedicated to the memory of Professor Teng Ma, director of the cell and tissue engineering laboratory at FAMU-FSU College of Engineering, who suddenly passed away in May of 2019. S.C.G. acknowledges funding from NIH (RO1-NS102395). S.H. thanks NIH for financial support through a Ruth Kirschstein National Research Service Award (F31 NS115409).

Funding

S.C.G. acknowledges funding from NIH (RO1-NS102395). S.H. thanks NIH for financial support through a Ruth Kirschstein National Research Service Award (F31 NS115409). The National High Magnetic Field Laboratory is supported by the National Science Foundation through the NSF (DMR-1644779) and State of Florida.

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Author notes

  1. Shannon Helsper and F. Andrew Bagdasarian contributed equally to this work.

Authors and Affiliations

  1. National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA

    Shannon Helsper, F. Andrew Bagdasarian, Jens T. Rosenberg & Samuel C. Grant

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

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

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

    Kaya Xu, Jea-Young Lee & Cesario V. Borlongan

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  1. Shannon Helsper
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Contributions

All authors designed the study and critically revised and approved the final version of the manuscript. S.H and F.A.B. contributed equally to this manuscript. S.H. performed surgeries with assistance from J.T.R. S.H. and F.A.B. performed behavioral assessment, MRI scans, data analysis, and statistical analysis and wrote the manuscript, with editing by S.C.G. X.Y. performed cell culture work under the supervision of T.M. K.X. and J.Y.L performed histological assessment under the supervision of C.V.B. S.C.G, C.V.B, T.M, and J.T.R conceived the project.

Corresponding author

Correspondence to Samuel C. Grant.

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Ceasar Borlongan serves on the editorial board of Translational Stroke Research. All other authors report no conflicts of interest with respect to this work.

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Helsper, S., Bagdasarian, F.A., Yuan, X. et al. Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1 T. Transl. Stroke Res. 13, 543–555 (2022). https://doi.org/10.1007/s12975-021-00976-4

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