Promoted regeneration of transected facial nerve branches using mesenchymal stromal cells in relationship with apoptosis: 9-month results

Abstract

Objective: Our purpose is to investigate 9-month results of allogeneic mesenchymal stromal cells (MSCs) application on the anastomosed nerve and to make a comparison of nerve regeneration between anastomosis+MSCs application and anastomosis only. Additionally, an association was sought between histologic outcome and level of apoptotic activity at 9th month. Materials and Methods: The study was carried out in three rats. The right buccal branch was anastomosed with sutures following complete transection, and the anastomosis site was treated with homologous MSCs. The right marginal mandibular branch was left intact, but it was in contact with MSCs. The left buccal branch was transected and anastomosed in a similar manner except for MSCs application. The left side marginal mandibular branch was left intact. At month 9, the surgical field was re-explored. Two nerve samples from four facial nerve branches, each 0.5 mm in length, were taken from distal to the anastomosis site, one for apoptosis and the other for histologic examination. Apoptosis was investigated and scored in two rats using TUNEL assay. Results: The histologic examination displayed regularly spaced axons with myelin sheath of appropriate thickness in intact nerve segments and nerve segments in contact with MSCs. Samples from those nerves anastomosed only and those anastomosed+MSCs treatment consisted of grouping axons in different size. These axons were enveloped by myelin sheath of some thickness. Quantitative measurements of axon diameter and myelin thickness compared favorably with those nerves anastomosed+ MSCs treatment versus anastomosed only. However, the difference between the two was not apparent as previous months. Intensity of apoptosis at month 9 was not found to correlate with histologic outcome, injury and use of MSCs. Conclusion: This 9-month study confirmed that use of MSCs in an anastomosed nerve promoted axonal regeneration and myelination. Apoptosis at month 9 does neither relate to histologic outcome nor use of MSC and previous injury. © The Mediterranean Society of Otology and Audiology.