Promotion of neurological recovery in rat spinal cord injury by mesenchymal stem cells loaded on nerve-guided collagen scaffold through increasing alternatively activated macrophage polarization.

Mesenchymal stem cells (MSCs) are characterized by multidifferentiation and immunoregulatory potential and have been used in the treatment of spinal cord injury (SCI), but direct transplantation may limit effectiveness due to their quick diffusion. The role of macrophages in healing is being increasingly recognized because of their ability to polarize into pro- and anti-inflammatory phenotypes. In the present study, nerve-guide collagen scaffold (CS) combined with rat MSCs was developed. After CS was confirmed to minimize MSC distribution in vivo by positron emission tomography (PET) imaging, the repair capacity of combined implantation of CS and MSCs and the effect on classically activated macrophage/alternatively activated macrophage (M2) polarization was assessed in a hemisected SCI rat model. In vivo studies showed that, compared to the control group, the rats in the combined implantation group exhibited more significant recovery of nerve function evidenced by the 21-point Basso-Beattie-Bresnahan score and footprint analysis. Morphological staining showed less macrophage infiltration, apoptosis and glial fibrillary acidic protein, and more neurofilaments, and the fibres were guided to grow through the implant. More M2 were observed in the combined implantation group. The data suggest that the combined implantation could support MSCs to play a protective role of SCI, not only through inhibiting chronic scar formation and providing linear guidance for the nerve, but also benefitting M2 polarization to form an anti-inflammatory environment. Thus, the combination of biomaterial and MSCs might be a prominent therapeutic treatment for SCI.