Polydatin promotes the neuronal differentiation of bone marrow mesenchymal stem cells in vitro and in vivo: Involvement of Nrf2 signalling pathway

Abstract

Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising repair strategy following spinal cord injury (SCI), although the therapeutic effects are minimal due to their limited neural differentiation potential. Polydatin (PD), a key component of the Chinese herb Polygonum cuspidatum, exerts significant neuroprotective effects in various central nervous system disorders and protects BMSCs against oxidative injury. However, the effect of PD on the neuronal differentiation of BMSCs, and the underlying mechanisms remain inadequately understood. In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 μmol/L) markedly facilitated BMSC differentiation into neuron-like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites. Furthermore, compared with either monotherapy, the combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function. Taken together, PD augments the neuronal differentiation of BMSCs via Nrf2 activation and improves functional recovery, indicating a promising new therapeutic approach against SCI.

Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by reducing oxidative stress, apoptosis, and inflammatory response

“…The model of SCI was induced under sterile conditions and performed according to Allen’s method as previously described [ 23 ]. Before surgery, the mice were anesthetized using 1% pentobarbital sodium (50 mg/kg) by intraperitoneal injection (i.p.…”

Electroacupuncture facilitates the integration of a grafted TrkC‐modified mesenchymal stem cell‐derived neural network into transected spinal cord in rats via increasing neurotrophin‐3

“…Mesenchymal stem cells (MSCs), which are easy to obtain, ethically uncomplicated, and relatively safe, have emerged as a promising candidate for SCI treatment, with the potential to differentiate into neuron‐like cells. Although this approach remains controversial, experimental evidence has suggested that MSCs, after suitable modifications, can display phenotypic and functional neuronal properties 6,7 . We have previously reported that an MSC‐derived neural network (MN) implantation strategy was able to facilitate the recovery of limb motor function in a rat model following thorough spinal cord transection 8 .…”

SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model

“…Among the different stem cell sources available, MSC is an abundant source of immature immune cells, with no ethical concerns [14,25]. They can be easily acquired, maintained, expanded quickly, and differentiated into neural cell types in vitro and in vivo [26,27]. No invasive procedures are required to obtain bone marrow-derived MSCs, and it has been safely used clinically.…”