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

Abstract

Aims This study was aimed to investigate whether electroacupuncture (EA) would increase the secretion of neurotrophin‐3 (NT‐3) from injured spinal cord tissue, and, if so, whether the increased NT‐3 would promote the survival, differentiation, and migration of grafted tyrosine kinase C (TrkC)‐modified mesenchymal stem cell (MSC)‐derived neural network cells. We next sought to determine if the latter would integrate with the host spinal cord neural circuit to improve the neurological function of injured spinal cord. Methods After NT‐3‐modified Schwann cells (SCs) and TrkC‐modified MSCs were co‐cultured in a gelatin sponge scaffold for 14 days, the MSCs differentiated into neuron‐like cells that formed a MSC‐derived neural network (MN) implant. On this basis, we combined the MN implantation with EA in a rat model of spinal cord injury (SCI) and performed immunohistochemical staining, neural tracing, electrophysiology, and behavioral testing after 8 weeks. Results Electroacupuncture application enhanced the production of endogenous NT‐3 in damaged spinal cord tissues. The increase in local NT‐3 production promoted the survival, migration, and maintenance of the grafted MN, which expressed NT‐3 high‐affinity TrkC. The combination of MN implantation and EA application improved cortical motor‐evoked potential relay and facilitated the locomotor performance of the paralyzed hindlimb compared with those of controls. These results suggest that the MN was better integrated into the host spinal cord neural network after EA treatment compared with control treatment. Conclusions Electroacupuncture as an adjuvant therapy for TrkC‐modified MSC‐derived MN, acted by increasing the local production of NT‐3, which accelerated neural network reconstruction and restoration of spinal cord function following SCI.

Electro‐acupuncture and its combination with adult stem cell transplantation for spinal cord injury treatment: A summary of current laboratory findings and a review of literature

“…Although these transdifferentiated cells are neuron‐like, they express most neuron markers including cytoskeleton proteins (neurofilament [NF]‐200, NF‐H, microtubule‐associated protein [MAP]2, and β‐tubulin III); synaptic structure proteins (postsynaptic density [PSD]‐95 and synaptophysin); neurotransmitters (γ‐aminobutyric acid [GABA] and choline acetyltransferase [ChAT]); and doublecortin (DCX). We have also shown that some of the TrkC gene‐modified MSC‐derived cells exhibit electrophysiologic properties in vitro, such as postsynaptic currents and action potentials in the presence of Schwann cells overexpressing NT‐3 93,95 . Importantly, the cells form extensive connections or contacts with host neurons and descending 5‐HT‐positive nerve fibers.…”

“…Previous researches have showed that the MSC-derived neuron-like cells in the injury/graft site of spinal cord were integrated into the host neural circuitry; therefore, they can receive neural input from the rostral and caudal areas of the injury/graft site in the transected SC and transmit the information to host neurons on both sides of the gap (Figure 3). 3,93 As reported previously, the aim of the this particular strategy is to induce the transdifferentiation of TrkC gene-modified MSCs into neuron-like cells that can serve as a relay mechanism upon transplantation into a gap in the SC. [94][95][96] To sum up, these processes promoted the regeneration of SC tissue and improved motor function in paralyzed limbs.…”

“…Showing two pattern diagrams of the location of the GV‐EA, taken from Yang Yang et al, CNS Neurosci Ther (2021) 93 . (A) A pattern diagram indicates selected electro‐acupuncture acupoints located at GV in rat.…”

Effect of Schwann cell transplantation combined with electroacupuncture on axonal regeneration and remyelination in rats with spinal cord injury

“…Co-transplantation of SCs with other cell types, including olfactory-ensheathing cells (Fouad et al, 2005), neural stem cells/progenitors (Niapour et al, 2012), and bone marrow mesenchymal stromal cells (MSC), can improve the repair of spinal cord injury because the cell types play complementary functions (Pourheydar et al, 2012). Interestingly, Ding et al transplanted SCs-MSC-derived neural network implant combined with EA in rats, which can accelerate neural network reconstruction and restoration of spinal cord function following SCI (Yang et al, 2021).…”

Acupuncture in Patients with Spinal Cord Injuries: Mobilization of Potential Neuroprogenitors and Clinical Outcome in a Case Series

“…In Asia, acupuncture is applied regularly in neurological diseases and injuries including SCI [30]. Recent studies demonstrated that acupuncture induced rodent neuroregeneration after brain damage and an increase in the number of motor neurons accompanied by increased expression of glia-derived neurotrophic factor in the spinal cord [31,32] and facilitated the integration of a grafted neural network [33]. Obviously, electroacupuncture downregulates proapoptotic signals and upregulates antiapoptotic proteins like Bcl-2 [34].…”