The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats

Abstract

Inflammatory response following spinal cord injury (SCI) is important in regulation of the repair process. Olfactory ensheathing cells (OECs) and Schwann cells (SCs) are important donor cells for repairing SCI in different animal models. However, synergistic or complementary effects of co-transplantation of both cells for this purpose have not been extensively investigated. In the present study, we investigated the effects of co-transplantation of OECs and SCs on expression of pro- or anti-inflammatory factor and polarization of macrophages in the injured spinal cord of rats. Mixed cell suspensions containing OECs and SCs were transplanted into the injured site at 7 days after contusion at the vertebral T10 level. Compared with the DMEM, SC, or OEC group, the co-transplantation group had a more extensive distribution of the grafted cells and significantly reduced number of astrocytes, microglia/macrophage infiltration, and expression of chemokines (CCL2 and CCL3) at the injured site. The co-transplantation group also significantly increased arginase/CD206 macrophages (IL-4) and decreased iNOS/CD16/32 macrophages (IFN-γ), which was followed by higher IL-10 and IL-13 and lower IL-6 and TNF-α in their expression levels, a smaller cystic cavity area, and improved motor functions. These results indicate that OEC and SC co-transplantation could promote the shift of the macrophage phenotype from M(IFN-γ) to M(IL-4), reduce inflammatory cell infiltration in the injured site, and regulate inflammatory factors and chemokine expression, which provide a better immune environment for SCI repair.

Intrathecal transplantation of olfactory ensheathing cells by lumbar puncture for thoracic spinal cord injury in mice

“…30,31 OECs can significantly reduce the expression of CCL2 and CCL3, reducing the activation of astrocytes, which leads to scar repair. 24 In addition, this study also showed that intrathecal grafted OECs resulted in substantial improvement in motor function by higher open-field BMS score. This is the "golden standard" to prove a therapy method is effective.…”

“…[21][22][23] As SCI induces apoptosis or death of neurons and scar formation, we examined neuron regeneration and scar bridging to evaluate the therapeutic efficacy of LP-transplanted OECs. [24][25][26] Figure 3 shows that the number of endogenous neurons, from −400 to +400 µm, in OEC-transplanted mice is more than that in SCI mice without engraftment. Intrathecal transplanted OECs could promote neuron regeneration in this range.…”

Time is spine: a review of translational advances in spinal cord injury

“…OECs are highly phagocytic cells that surround olfactory neurons and rapidly clear pathogens and debris at the CNS-nasal mucosa border. 38,152,178,188 They also generate a favorable environment by expressing neurotrophins and facilitating olfactory regeneration after injury. 9 OECs have been harvested from the olfactory bulb and the nasal mucosa for transplant into the cord.…”

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

“…These results suggest that OECs and SC's co-transplantation can promote the change of the macrophage phenotype from M1 secreting IFN-γ, to M2 secreting IL-4. The induction to M2 reduces ICs infiltration in the damaged site, regulates inflammatory factors and chemokine expression, which provide ICs environment for SCI repair [65].…”