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The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury

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Abstract

Background

Neonatal hypoxia ischemia causes severe brain damage. Stem cell therapy is a promising method for treating neuronal diseases. Clinical translation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the recovery of neurons after hypoxic ischemic encephalopathy (HIE) may represent an effective therapy.

Methods

Primary neurons were exposed to oxygen–glucose deprivation (OGD) and subsequently cocultured with UC-MSCs. Apoptosis was examined by Annexin V-FITC-PI. Genes related to apoptosis were detected using RT-PCR and western-blot analyses. Using an in vivo model, HIE was induced in postnatal day 7 mice, and UC-MSCs were transplanted via the intraventricular route. UC-MSC migration was investigated by immunofluorescence, and lesion volumes were measured by TTC staining. Apoptosis in injured brain cells was detected by the TUNEL assay. RT-PCR and ELISA were used to detect the expression of inflammatory factors in cells and animal tissues.

Results

Flow cytometry analysis revealed that apoptosis in injured neurons was inhibited by UC-MSCs. The RT-PCR and western blot results indicated that coculture inhibited the expression of proapoptotic genes and upregulated expression of antiapoptotic genes. In the animal model, transplanted UC-MSCs migrated toward the cerebral lesion site and decreased the lesion extent in HIE. TUNEL staining showed that the MSC group exhibited significantly reduced numbers of TUNEL-positive cells. RT-PCR and ELISA showed that UC-MSCs inhibited the upregulation of TNF-α and IL-1β in response to hypoxic ischemic injury.

Conclusion

These results indicate that UC-MSCs exert neuroprotective effects against hypoxic ischemic injury by inhibiting apoptosis, and the mechanism appears to be through alleviating the inflammatory response.

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Funding

This work was supported by Grants from the National Nature Science Foundation of China (No. 81200950), the Science and Technology Development Project of Shandong Province (No. 2014GSF118173), the Chinese Postdoctoral Science Foundation (No. 2016M590637), and Nature Science Foundation of Shandong province (ZR2019PH055).

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Authors and Affiliations

  1. Laboratory of Cell Therapy and Translational Medicine, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, China

    Fang Li, Kun Zhang, Hua Liu, Dong-Jie Xiao & Yun-Shan Wang

  2. Shandong Research Center of Transplantation and Tissue, Jinan, 250013, China

    Fang Li, Kun Zhang, Hua Liu, Dong-Jie Xiao & Yun-Shan Wang

  3. Clinical Laboratory, The People’s Hospital of Bozhou, Bozhou, 236800, China

    Tan Yang

Authors
  1. Fang Li
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  2. Kun Zhang
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  3. Hua Liu
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  4. Tan Yang
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  5. Dong-Jie Xiao
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  6. Yun-Shan Wang
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Contributions

FL cultured the cell lines and performed the experiments in vitro. KZ detected the gene and protein expression in animal tissue. HL devised the protocol and wrote the manuscript. Tan Yang contributed to the animal model. DX conceived the original idea and supervised the experiments. YW approved the final version. The manuscript represents our original unpublished research results and did not submitting to other journals.

Corresponding author

Correspondence to Hua Liu.

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Ethical approval

Informed content was obtained from family members of the newborns and the experimental protocol was approved by the Ethics Committee of Jinan central Hospital.

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No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

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Li, F., Zhang, K., Liu, H. et al. The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury. World J Pediatr 16, 193–200 (2020). https://doi.org/10.1007/s12519-019-00310-x

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  • DOI: https://doi.org/10.1007/s12519-019-00310-x

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