Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection

Abstract

Background Severe peripheral nerve injury significantly affects patients’ quality of life and induces neuropathic pain. Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Methods Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. Results Catwalk gait analysis showed that animals in the NCSC group exhibited a higher stand index and Max intensity At (%) relative to those that received the cell-free scaffold (scaffold group) (p < 0.05). The mechanical and thermal allodynia in the medial-plantar surface of the ipsilateral hind paw were significantly relieved in the NCSC group. Sunitinib (SNT)-induced upregulation of glial fibrillary acidic protein (GFAP) (astrocyte) and ionized calcium-binding adaptor molecule 1 (Iba-1) (microglia) in the ipsilateral L4–5 dorsal and ventral horn relative to the contralateral side. Immunofluorescence analyses revealed decreased astrocyte and microglia activation. Activation of ERK and NF-κB signals and expression of transient receptor potential vanilloid 1 (TRPV1) expression were downregulated. Conclusion NCSC-laden nerve scaffolds mitigated SNT-induced neuropathic pain and improved motor function recovery after sciatic nerve repair. NCSCs also protected the spinal cord from SNT-induced glial activation and central sensitization.

Biomimetic Strategies for Peripheral Nerve Injury Repair: An Exploration of Microarchitecture and Cellularization

“…For example, in a rat sciatic nerve model, Lv et al found that NCSC promoted regeneration and reconstruction of a transected sciatic nerve by seeding NCSC in a PLLA electrospun conduit [140]. More recently, NCSC-laden nerve scaffolds were shown to attenuate nerve sciatic transection pain, improve motor function recovery, and protect spinal cord from glial activation [141]. An important consideration is whether transplanted cells have the potential to elicit inflammatory host immune responses.…”

Spinal Cord Injury Management through the Combination of Stem Cells and Implantable 3D Bioprinted Platforms

“…Moreover, the formation of synapses and regeneration of axons could be promoted after stem cell transplantation via the interactions between stem cells and the surrounding tissues. This could also modify the injury site microenvironment and accelerate the growth of the neural axon by generating some neurotrophic growth factors [28]. Transplanted stem cells could also enhance the myelin formation around neural axons, both newly grown and previous ones, by differentiating into gliocytes and oligodendrocytes.…”

Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway

“…Enhanced function symptoms performed hypersensitivity (nonstimulating pain and increased pain sensitivity), while dysfunction symptoms were mainly manifested as tactile and thermal hyposensitivity, and in the advanced stages, patients may even develop complete loss of sensation [ 6 ]. Among the various neuropathic symptoms, cardiac autonomic neuropathy may result in sudden death, abnormal pain seriously affects the patient's comfort, and pain insensitivity leads to the high risk of burns, trauma and ulcers, eventually leading to amputation [ 7 ].…”

“…Studies demonstrated that stem cell transplantation partially repaired damaged neurons and delayed the progress of amyloidosis in the treatment of Alzheimer's disease [ 8 ]. Stem cell treatment also promoted the repair of the injured plane in the treatment of transverse nerve injury caused by trauma [ 7 ]. Importantly, compared with other treatment options, stem cell transplantation can reverse neuropathy, which may be associated with high proliferation and differentiation of stem cells; also the specific mechanism remains unclear [ 12 ].…”