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Reprogramming of astrocytes to neuronal-like cells in spinal cord injury: a systematic review

Spinal Cord volume 62, pages 133–142 (2024)Cite this article

Subjects

Abstract

Study design

A Systematic Review

Objectives

To determine the therapeutic efficacy of in vivo reprogramming of astrocytes into neuronal-like cells in animal models of spinal cord injury (SCI).

Methods

PRISMA 2020 guidelines were utilized, and search engines Medline, Web of Science, Scopus, and Embase until June 2023 were used. Studies that examined the effects of converting astrocytes into neuron-like cells with any vector in all animal models were included, while conversion from other cells except for spinal astrocytes, chemical mechanisms to provide SCI models, brain injury population, and conversion without in-vivo experience were excluded. The risk of bias was calculated independently.

Results

5302 manuscripts were initially identified and after eligibility assessment, 43 studies were included for full-text analysis. After final analysis, 13 manuscripts were included. All were graded as high-quality assessments. The transduction factors Sox2, Oct4, Klf4, fibroblast growth factor 4 (Fgf4) antibody, neurogenic differentiation 1 (Neurod1), zinc finger protein 521 (Zfp521), ginsenoside Rg1, and small molecules (LDN193189, CHIR99021, and DAPT) could effectively reprogramme astrocytes into neuron-like cells. The process was enhanced by p21-p53, or Notch signaling knockout, valproic acid, or chondroitin sulfate proteoglycan inhibitors. The type of mature neurons was both excitatory and inhibitory.

Conclusion

Astrocyte reprogramming to neuronal-like cells in an animal model after SCI appears promising. The molecular and functional improvements after astrocyte reprogramming were demonstrated in vivo, and further investigation is required in this field.

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Fig. 1: PRISMA 2020 Flowchart for New Systematic Review.

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Data availability

All datasets for this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was Acknowledged and funded by the Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences [grant number is 99-2-93-49972].

Author information

Authors and Affiliations

  1. Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Danial Alizadeh, Mohammad-Rasoul Jalalifar, Zahra Ghodsi, Hamid Malekzadeh, Kurosh Mojtabavi, Sina Shool, Rasoul Masoomi & Vafa Rahimi-Movaghar

  2. Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Seyed Danial Alizadeh & Mohammad-Rasoul Jalalifar

  3. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Zahra Ghodsi, Hamid Malekzadeh & Vafa Rahimi-Movaghar

  4. Department of neurosurgery, Lorestan University of medical sciences, Khoram-Abad, Iran

    Mohsen Sadeghi-Naini

  5. Department of Cellular and Molecular Biology, University of Science and Culture, Tehran, Iran

    Golnoosh Rahimi

  6. Department of Stem Cell and Developmental Biology, Cell Science Research Center, ROYAN Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Golnoosh Rahimi & Sahar Kiani

  7. Department of Brain and Cognitive Sciences, Cell Science Research Center, ROYAN Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Golnoosh Rahimi & Sahar Kiani

  8. Neuroscience Department, Erasmus MC, Rotterdam, The Netherlands

    Kurosh Mojtabavi

  9. Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sina Shool

  10. Department of Management, Faculty of Social Sciences and Economics, Alzahra University, Tehran, Iran

    Zahra Eskandari

  11. Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA

    James Harrop

  12. Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Vafa Rahimi-Movaghar

  13. Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Vafa Rahimi-Movaghar

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  1. Seyed Danial Alizadeh
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Contributions

VRM conceived the presented idea and supervised the project. Z.G. revised the manuscript and communicated with team members and the corresponding author. SDA was responsible for writing the protocol and report, screening potentially eligible studies, extracting and analyzing data, interpreting results, assessing the risk of bias of included studies, creating tables and figures, discussing the results, and manuscript drafting. HM, GR, KM, MRJ and SS contributed to screening potentially eligible studies and extracting data. JH and SK were responsible for revising the manuscript and providing critical feedback. MSN analyzed and interpreted the data and results. ZE and RM conducted the database searches.

Corresponding author

Correspondence to Vafa Rahimi-Movaghar.

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Competing interests

The authors declare no competing interests.

Ethical approval

The Ethics Committee of Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, approved the study, and the reference number is IR.TUMS.SINAHOSPITAL.REC.1399.114.

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Alizadeh, S.D., Jalalifar, MR., Ghodsi, Z. et al. Reprogramming of astrocytes to neuronal-like cells in spinal cord injury: a systematic review. Spinal Cord 62, 133–142 (2024). https://doi.org/10.1038/s41393-024-00969-8

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