Oligodendrocyte Progenitor Cell Transplantation Ameliorates Preterm Infant Cerebral White Matter Injury in Rats Model

Zhaoyan Wang; Leping Zhang; Yinxiang Yang; Qian Wang; Suqing Qu; Xiaohua Wang; Zhixu He; Zuo Luan

doi:10.2147/NDT.S414493

Oligodendrocyte Progenitor Cell Transplantation Ameliorates Preterm Infant Cerebral White Matter Injury in Rats Model

Neuropsychiatr Dis Treat. 2023 Sep 11:19:1935-1947. doi: 10.2147/NDT.S414493. eCollection 2023.

Authors

Zhaoyan Wang^#¹, Leping Zhang^#^{1

2}, Yinxiang Yang¹, Qian Wang¹, Suqing Qu¹, Xiaohua Wang¹, Zhixu He^{2

3}, Zuo Luan¹

Affiliations

¹ Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People's Republic of China.
² Guizhou Medical University, Guiyang, 550004, People's Republic of China.
³ Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563100, People's Republic of China.

^# Contributed equally.

Abstract

Background: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs).

Methods: This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2⁺/NG2⁺/PDGFRα⁺/O4⁺ hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function.

Results: Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery.

Conclusion: Our study showed that exogenous hOPCs could differentiate into CC1⁺ OLS in the brain of WMI rats, improving their cognitive functions.

Keywords: cell replacement therapy; cerebral white matter injury; oligodendrocyte progenitor cells; preterm infant; rat model.

Grants and funding

The National Key R&D Program of China supported this work [2018YFA0108601]. The funding source had no role in the study’s design, collection, analysis, interpretation of data, or writing of the manuscript.