Research Paper Volume 13, Issue 6 pp 9056—9070

Transplantation of olfactory ensheathing cells promotes the therapeutic effect of neural stem cells on spinal cord injury by inhibiting necrioptosis

Xiaoyu Wang1,2, , Naifeng Kuang2, , Yuexia Chen2, , Guifeng Liu2, , Nan Wang2, , Fan’er Kong3, , Shouwei Yue1, , Zuncheng Zheng2, ,

  • 1 Rehabilitation Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
  • 2 Department of Rehabilitation, Taian City Central Hospital, Taian 271000, Shandong, China
  • 3 Shandong First Medical University and Shandong Academy of Medical Science, Taian 271000, Shandong, China

Received: May 27, 2020       Accepted: January 13, 2021       Published: March 4, 2021
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Transplantation of neural stem cells (NSCs) is one of the most promising treatments for spinal cord injury (SCI). However, the limited survival of transplanted NSCs reduces their therapeutic effects. The aim of the present study was to examine whether a co-transplantation of olfactory ensheathing cells (OECs) may enhance the survival of NSCs and improve the beneficial effects of NSCs in rats with SCI, as well as to investigate potential mechanisms underlying such efficacies. Co-transplantation of OECs and NSCs was used to treat rats with SCI. Sympathetic nerve function was determined by measuring sympathetic skin responses. The results showed that OEC/NSC co-transplantation improved motor function and autonomic nerve function in rats with SCI. Co-transplantation of OECs promoted NSC-induced neuroprotection and inhibited programmed necrosis of NSCs, which was mediated by receptor-interacting protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). Furthermore, OECs increased the proliferation and differentiation of NSCs in vitro, and improved the survival rate of NSCs in vivo. Taken together, we conclude that transplantation of OECs inhibited programmed necrosis of co-transplanted NSCs to promote therapeutic effects on SCI. Therefore, co-transplantation of OECs and NSCs may represent a promising strategy for treating patients with SCI.


OEC: olfactory ensheathing cell; NSC: neural stem cell; SCI: spinal cord injury; RIP3: receptor-interacting protein kinase 3; MLKL: mixed lineage kinase domain-like protein; NPCs: neural progenitor cells; GFAP: glial fibrillary acidic protein; P75: nerve growth factor receptor p75; DAPI: 4′,6- diamidino-2-phenylindole. PBS: phosphate-buffered saline; DMEM: Dulbecco’s modified eagle medium; FCS: fetal calf serum; OEC-CM: OEC serum-free conditioned medium; BBB: the Basso, Beattie, and Bresnahan 21-point open-field locomotor rating scale; SSR: sympathetic skin responses; NF200: neurofilament 200; HE: hematoxylin and eosin; ANOVA: analysis of variance.