Intrauterine desensitization enables long term survival of human oligodendrocyte progenitor cells without immunosuppression

Dou Ye; Suqing Qu; Yinxiang Yang; Zhaoyan Wang; Qian Wang; Weipeng Liu; Fan Zhang; Qian Guan; Xiaohua Wang; Jing Zang; Xin Li; Hengtao Liu; Ruiqin Yao; Zhichun Feng; Zuo Luan

doi:10.1016/j.isci.2023.106647

Intrauterine desensitization enables long term survival of human oligodendrocyte progenitor cells without immunosuppression

iScience. 2023 Apr 11;26(5):106647. doi: 10.1016/j.isci.2023.106647. eCollection 2023 May 19.

Authors

Dou Ye^{1

2}, Suqing Qu¹, Yinxiang Yang¹, Zhaoyan Wang¹, Qian Wang¹, Weipeng Liu¹, Fan Zhang^{1

2}, Qian Guan¹, Xiaohua Wang¹, Jing Zang¹, Xin Li¹, Hengtao Liu³, Ruiqin Yao⁴, Zhichun Feng⁵, Zuo Luan^{1

2}

Affiliations

¹ Department of Pediatrics, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing 100037, China.
² Medical School of Chinese PLA, Beijing 100853, China.
³ Jiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing 100191, China.
⁴ Department of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China.
⁵ Faculty of Pediatrics, The Seventh Medical Centre, Chinese PLA General Hospital, 100700 Beijing, China.

Abstract

Immune rejection can be reduced using immunosuppressants which are not viable for premature infants. However, desensitization can induce immune tolerance for premature infants because of underdeveloped immune system. The fetuses of Wistar rats at 15-17 days gestation were injected via hOPCs-1 into brain, muscles, and abdomen ex utero and then returned while the fetuses of control without injection. After 6 weeks of desensitization, the brain and muscles were transplanted with hOPCs-1, hNSCs-1, and hOPCs-2. After 10 and 34 weeks of desensitization, hOPCs-1 and hNSCs-1 in desensitized groups was higher than that in the control group while hOPCs-2 were rejected. Treg, CD4CD28, CD8CD28, and CD45RC between the desensitization and the control group differed significantly. Inflammatory cells in group with hOPCs-1 and hNSCs-1 was lower than that in the control group. hOPCs-1 can differentiate into myelin in desensitized groups. Wistar rats with desensitization developed immune tolerance to desensitized and transplanted cells.

Keywords: Immunology; Neurology; Stem cells research.