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Glia-Like Cells from Late-Passage Human MSCs Protect Against Ischemic Stroke Through IGFBP-4

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Abstract

Stem cell therapy is considered to be a promising future treatment for intractable neurological diseases, although all the clinical trials using stem cells have not yet shown any good results. Early passage mesenchymal stem cells (MSCs) have been used in most clinical trials because of the issues on safety and efficacy. However, it is not easy to get plenty of cells enough for the treatment and it costs too much. Lots of late passage MSCs can be obtained at lower cost but their efficacy would be a big hurdle for clinical trials. If late passage MSCs with better efficacy could be used in clinical trials, it could be a new and revolutionary solution to reduce cost and enhance easier clinical trials. In the present study, it was investigated whether late passage MSCs could be induced into glia-like cells (ghMSCs); ghMSCs had better efficacy and they protected neurons and the brain from ischemia, and insulin-like growth factor binding protein-4 (IGFBP-4) played a critical role in beneficial effect of ghMSCs. ghMSCs were induced from MSCs and treated in in vitro and in vivo models of ischemia. They effectively protected neurons from ischemia and restored the brain damaged by cerebral infarction. These beneficial effects were significantly blocked by IGFBP-4 antibody. The current study demontsrated that late passage hMSCs can be efficiently induced into ghMSCs with better neuroprotective effect on ischemic stroke. Moreover, the results indicate that IGFBP-4 released from ghMSCs may serve as one of the key neuronal survival factors secreted from ghMSCs.

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Funding

This research was supported by a grant from 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 (grant number HI17C2160).

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Author notes

  1. Jeong Woo Son and Jihye Park contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Hanyang University College of Medicine, Gyeongchun-ro, Guri-Si, 11923, Gyeonggi-do, Republic of Korea

    Jeong-Woo Son, Ye Eun Kim & Seong-Ho Koh

  2. Laboratory of Stem Cell & Neurobiology, Department of Oral Anatomy, Dental Research Institute and School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea

    Jihye Park, Jieun Ha & Mi-Sook Chang

  3. Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Gyeongchun-ro, Guri-Si, 11923, Gyeonggi-do, Republic of Korea

    Ye Eun Kim & Seong-Ho Koh

  4. Department of Radiology, Hanyang University College of Medicine, Seoul, 04763, Republic of Korea

    Dong Woo Park

  5. Neuroscience Research Institute, Seoul National University, Seoul, 03080, Republic of Korea

    Mi-Sook Chang

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  1. Jeong-Woo Son
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Correspondence to Mi-Sook Chang or Seong-Ho Koh.

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Son, JW., Park, J., Kim, Y.E. et al. Glia-Like Cells from Late-Passage Human MSCs Protect Against Ischemic Stroke Through IGFBP-4. Mol Neurobiol 56, 7617–7630 (2019). https://doi.org/10.1007/s12035-019-1629-8

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