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    Promoted regeneration of transected facial nerve branches using mesenchymal stromal cells in relationship with apoptosis: 9-month results
    (2010) Satar B.; Oztas E.; Hidir Y.; Erdogan E.; Kucuktag Z.; Oguztuzun S.; Safali M.
    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.
  • [ X ]
    Öğe
    Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells
    (Elsevier Inc., 2012) Satar B.; Hidir Y.; Serdar M.A.; Kucuktag Z.; Ural A.U.; Avcu F.; Safali M.
    Background aims. The types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-? and transforming growth factor (TGF)-?1 in anastomosed facial nerves that had been treated with or without MSC. Methods. In seven rats, the buccal branch of the right facial nerve was transected, anastomosed and treated with MSC (anastomosed + MSC group). The left buccal branch was anastomosed only (anastomosed-only group). The left mandibular branch served as an intact nerve group. On days 1820, the distal segments of the branches were examined in terms of expression of the mentioned proteins and apoptosis scores using polymerase chain reaction (PCR) and terminal deoxynucleotidyl transferase-mediated digoxigenin-UTP nick end labeling (TUNEL) assays. Results. MSC application significantly increased CNTF, PDGF-?, LIF, TGF-?1, BDNF and NT-3 expression (P < 0.05). MAG expression slightly decreased whereas NCAM-1, MMP-1A and FGF-2 slightly increased(P > 0.05). Changes in other proteins and apoptosis scores were not significant. Conclusions. These results suggest that MSC increases expression of CNTF, PDGF-?, LIF,TGF-?1, BDNF and NT-3. MAG, NCAM-1, MMP-1A and FGF-2 expressions were slightly changed in this stage of nerve regeneration. The comparison of apoptotic activity was not conclusive. Overall, it appears that MSC might have differential effects on the mentioned tissue-related proteins and trophic/growth factors. © 2012 Informa Healthcare.