Abstract
Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk-MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs were isolated from green fluorescence protein transgenic mice and then expanded and transplanted with PGA felt for the hybrid transplantation (HY group) into the RLN transected mouse model. Transplantation of culture medium (M group) and PGA + medium (PGA group) were examined as controls. After eight weeks, trans-oral video laryngoscopy demonstrated 80% recovery of spontaneous vocal-fold movement during breathing in the HY group, whereas the M and PGA groups showed wholly no recoveries. The Sk-MSCs showed active engraftment confined to the damaged RLN portion, representing favorable prevention of cell diffusion on PGA, with an enhanced expression of nerve growth factor mRNAs. Axonal re-connection in the HY group was confirmed by histological serial sections. Immunohistochemical analysis revealed the differentiation of Sk-MSCs into Schwann cells and perineurial/endoneurial cells and axonal growth supportive of perineurium/endoneurium. The number of axons recovered was over 86%. These results showed that the stem cell and cytokine delivery system using hybrid transplantation of Sk-MSCs/PGA-felt is a potentially practical and useful approach for the recovery of transected RLN.
Highlights
The recurrent laryngeal nerve (RLN) comprises two non-symmetrical branches of the vagus nerve looping under the aortic arch and the right subclavian artery, both traveling upwards alongside the trachea
We have proposed and demonstrated the significant therapeutic capacity of skeletal muscle-derived multipotent stem cell (Sk-MSC) and human skeletal muscle-derived stem cell (Sk-SC) transplantation to the transected sciatic nerve, showing high numerical and functional recovery [6,7]
The GFP+ cells/tissue closely adhered to the trachea, which was the area of the RLN transected (Figure 1A,B)
Summary
The recurrent laryngeal nerve (RLN) comprises two non-symmetrical branches of the vagus nerve looping under the aortic arch (left-side) and the right subclavian artery (right-side), both traveling upwards alongside the trachea. There is no effective treatment, and natural healing is not expected in human patients, impacting them functionally, physiologically, and emotionally. Bone marrow mesenchymal stem cells were applied intravenously in the rat RLN crash injury model and showed favorable functional recovery of vocal fold motion; direct contribution of these stem cells to nerve regeneration was unclear [5]. We have proposed and demonstrated the significant therapeutic capacity of skeletal muscle-derived multipotent stem cell (Sk-MSC) and human skeletal muscle-derived stem cell (Sk-SC) transplantation to the transected sciatic nerve, showing high numerical and functional recovery [6,7]. The purpose of this study was establishment of a novel method to obtain the morphological and functional regeneration of gap-transected RLN using hybrid-transplantation of the mouse Sk-MSCs and PGA felt
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