Stem Cells from Human Exfoliated Deciduous Teeth (SHED) Differentiate in vivo and Promote Facial Nerve Regeneration

Abstract

Post-traumatic lesions with transection of the facial nerve present limited functional outcome even after repair by gold-standard microsurgical techniques. Stem cell engraftment combined with surgical repair has been reported as a beneficial alternative. However, the best association between the source of stem cell and the nature of conduit, as well as the long-term postoperative cell viability are still matters of debate. We aimed to assess the functional and morphological effects of stem cells from human exfoliated deciduous teeth (SHED) in polyglycolic acid tube (PGAt) combined with autografting of rat facial nerve on repair after neurotmesis. The mandibular branch of rat facial nerve submitted to neurotmesis was repaired by autograft and PGAt filled with purified basement membrane matrix with or without SHED. Outcome variables were compound muscle action potential (CMAP) and axon morphometric. Animals from the SHED group had mean CMAP amplitudes and mean axonal diameters significantly higher than the control group (p < 0.001). Mean axonal densities were significantly higher in the control group (p = 0.004). The engrafted nerve segment resected 6 weeks after surgery presented cells of human origin that were positive for the Schwann cell marker (S100), indicating viability of transplanted SHED and a Schwann cell-like phenotype. We conclude that regeneration of the mandibular branch of the rat facial nerve was improved by SHED within PGAt. The stem cells integrated and remained viable in the neural tissue for 6 weeks since transplantation, and positive labeling for S100 Schwann-cell marker suggests cells initiated in vivo differentiation.

Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration

“…To investigate the most common expression pattern of positive markers in SHED, 20 publications were analyzed and summarized in Figure 2 [22,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65]. In 15 of them, CD73 was described to be expressed; the other expressed positive markers of SHED were CD90 (14) and CD105 (12).…”

Multidifferentiation potential of dental-derived stem cells

“…The lncRNA C21orf121 promotes SHED differentiation into neuronal cells by upregulating the expression of BMP2, acting as a competing endogenous RNA to compete with BMP2 binding to miR-140-5p[ 79 ]. SHED in polyglycolic acid tubes combined with autografting can regenerate the mandibular branch of the rat facial nerve[ 80 ]. Also, SHED have been used to repair a Parkinsonian rat model, an acute contused spinal cord injury model and a model of diabetic peripheral neuropathy[ 81 - 83 ].…”

Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies

“…If the facial nerve injury is severe, such as neurotmesis, the nerve does not spontaneously recover, and outcome is poor even after neurorrhaphy. In cases of extensive injury, autologous nerve graft, with or without nerve conduits, is considered the ‘gold-standard’ clinical technique [ 21 ]. In recent decades, considerable effort has been devoted to development of various synthetic and natural nerve-guidance conduits for improving peripheral nerve regeneration following injuries caused by small gaps.…”

“…Another study also compared an autograft alone with an autograft incorporating stem cells from human exfoliated deciduous teeth (SHED) in a rat model of facial nerve repair following nerve transection [ 21 ]. SHED was shown to induce local neoangiogenesis and differentiation into supporting cells such as Schwann cells, and promote axonal regeneration [ 21 ]. In addition, cultured SHED have been shown to produce a number of neurotrophic factors, including neural growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (BDNF).…”