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

Abstract

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.

Spinal cord injury: Olfactory ensheathing cell‐based therapeutic strategies

“…Recently, it was reported that an OEC‐conditioned medium could induce NSCs to differentiate into neurons, indicating that the combined transplantation of OECs and NSCs may be beneficial for regeneration (Ge et al., 2021). Indeed, many studies have examined whether co‐transplantation of OECs with other cells can make additional contributions to nerve regeneration (Wang, Kuang, et al., 2021).…”

“…NSCs may be beneficial for regeneration (Ge et al, 2021). Indeed, many studies have examined whether co-transplantation of OECs with other cells can make additional contributions to nerve regeneration (Wang, Kuang, et al, 2021).…”

The roles and applications of neural stem cells in spinal cord injury repair

“…Besides Schwann cells, OECs—the natural glial cells in the olfactory system—are another popular candidate as cograft cells, considering their potential to support neuronal survival and growth ( Reshamwala et al, 2019 ). Rat OECs can inhibit necroptosis of rat hippocampal NSCs as well as increase their survival, proliferation, and differentiation, leading to significant motor and autonomous improvement in a rat contusion SCI model at T10 level ( Wang X. et al, 2021 ).…”

Transplantation of Olfactory Ensheathing Cells: Properties and Therapeutic Effects after Transplantation into the Lesioned Nervous System

“…Another way to improve OECs' effects after transplantation is to associate them with other cell types. Interestingly, as described in part 7, many studies have reported the co-transplantation of OECs and additional cells in numerous lesion models such as PNI, SCI, Parkinson lesion model, hippocampus lesion model, intracerebral hemorrhage model or TBI [142,149,154,156,157,160,[172][173][174]. Mainly, OECs have been transplanted in addition to three different cell types: stem cells, SCs and differentiated neurons.…”