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Transplantation of PSA-NCAM-Positive Neural Precursors from Human Embryonic Stem Cells Promotes Functional Recovery in an Animal Model of Spinal Cord Injury

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Tissue Engineering and Regenerative Medicine Aims and scope

A Correction to this article was published on 26 October 2022

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Abstract

Background:

Spinal cord injury (SCI) results in permanent impairment of motor and sensory functions at and below the lesion site. There is no therapeutic option to the functional recovery of SCI involving diverse injury responses of different cell types in the lesion that limit endogenous nerve regeneration. In this regard, cell replacement therapy utilizing stem cells or their derivatives has become a highly promising approach to promote locomotor recovery. For this reason, the demand for a safe and efficient multipotent cell source that can differentiate into various neural cells is increasing. In this study, we evaluated the efficacy and safety of human polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (hNPCsPSA-NCAM+) as a treatment for SCI.

Methods:

One hundred thousand hNPCsPSA-NCAM+ isolated from human embryonic stem cell-derived NPCs were transplanted into the lesion site by microinjection 7 days after contusive SCI at the thoracic level. We examined the histological characteristics of the graft and behavioral improvement in the SCI rats 10 weeks after transplantation.

Results:

Locomotor activity improvement was estimated by the Basso–Beattie–Bresnahan locomotor rating scale. Behavioral tests revealed that the transplantation of the hNPCsPSA-NCAM+ into the injured spinal cords of rats significantly improved locomotor function. Histological examination showed that hNPCsPSA-NCAM+ had differentiated into neural cells and successfully integrated into the host tissue with no evidence of tumor formation. We investigated cytokine expressions, which led to the early therapeutic effect of hNPCsPSA-NCAM+, and found that some undifferentiated NPCs still expressed midkine, a well-known neurotrophic factor involved in neural development and inflammatory responses, 10 weeks after transplantation.

Conclusion:

Our results demonstrate that hNPCsPSA-NCAM+ serve as a safe and efficient cell source which has the potential to improve impaired motor function following SCI.

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Acknowledgements

We thank Mrs. S.J. Jung for technical assistance. This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI20C0168).

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Author notes

  1. Do-Hun Kim, Hyun-Ju Cho & Chul-Yong Park

    Present address: S.Biomedics Co., Ltd, 2nd Floor, 28 Seongsui-ro 26-gil, Seongdong-gu, Seoul, 04797, South Korea

Authors and Affiliations

  1. Department of Physiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Do-Hun Kim, Chul-Yong Park & Dong-Wook Kim

  2. Brain Korea 21 PLUS Program for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Do-Hun Kim & Dong-Wook Kim

  3. S.Biomedics Co., Ltd, 2nd Floor, 28 Seongsui-ro 26-gil, Seongdong-gu, Seoul, 04797, South Korea

    Myung Soo Cho & Dong-Wook Kim

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Contributions

D.-H. Kim Ph.D.: Conception and design, Collection and/or assembly of data, Data analysis and interpretation, Manuscript writing. H.-J. Cho MS: Collection and/or assembly of data, Data analysis and interpretation. C.-Y. Park Ph.D.: Collection and/or assembly of data, Data analysis and interpretation. M.S. Cho Ph.D.: Conception and design, Data analysis and interpretation, Manuscript writing and Final approval of manuscript. D.-W. Kim Ph.D.: Conception and design, Data analysis and interpretation, Manuscript writing and Final approval of manuscript.

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Correspondence to Myung Soo Cho or Dong-Wook Kim.

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All animal studies were done with the approval of the Institutional Animal Care and Use Committee of Yonsei University College of Medicine, Seoul, Korea (4-2015-1097).

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Kim, DH., Cho, HJ., Park, CY. et al. Transplantation of PSA-NCAM-Positive Neural Precursors from Human Embryonic Stem Cells Promotes Functional Recovery in an Animal Model of Spinal Cord Injury. Tissue Eng Regen Med 19, 1349–1358 (2022). https://doi.org/10.1007/s13770-022-00483-z

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