ABSTRACT
Peripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy. Methods Five millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F +T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis. Results The experiments indicated that sensory function improved when transgenic hESCs were used. The regeneration of sensory fibers indeed led to increased reflexes, upon stimulation of the paw ipsilateral to the lesion, as seen by von-Frey evaluation, which was supported by immunohistochemistry. Conclusions Overall, the present data demonstrated that transgenic embryonic stem cells, engineered to overexpress FGF-2 in an inducible fashion, could be employed to support regeneration aiming at the recovery of both motor and sensory functions.(AU)
Subject(s)
Animals , Male , Rats , Sciatic Nerve/transplantation , Transplantation, Heterologous/rehabilitation , Fibrin Tissue Adhesive , Embryonic Stem Cells , Nerve Regeneration , Mice, Inbred C57BLABSTRACT
As lesões ósseas têm a regeneração tecidual guiada (RTG) como uma possibilidade de tratamento, dependendo da morfologia do defeito. Esse procedimento visa selecionar células específicas usando uma membrana para a sua proliferação na área lesada. Entretanto, a regeneração completa do defeito pode não ser obtida, sendo a eliminação da doença o único resultado. O objetivo deste caso clínico foi avaliar o tratamento de um defeito interproximal, de duas paredes, pela técnica da RTG. Paciente GWS, 22 anos compareceu à clínica de Periodontia do SIOMS, queixando-se de sangramento gengival nos dentes 45 e 46. Após os exames clínico e radiográfico, verificou-se a presença de perda óssea interproximal nos referidos dentes, com profundidade de sondagem (PS) de 9mm e sangramento a sondagem (SS). Elaborou-se o plano de tratamento e seguiu-se tratamento periodontal não-cirúrgico. Sem sucesso na eliminação do problema, procedeu-se a RTG da área. A técnica realizada foi uma incisão intrassulcular, descolamento de um retalho total, debridamento, descontaminação química da raiz, inserção de um enxerto ósseo e de uma membrana absorvível xenógenos, reposicionamento do retalho e sutura. Fez-se o controle a cada 30 dias e, após 12 meses, a região demonstrou ausência de SS, redução da PS e aumento do nível clínico de inserção, porém, não viu-se a completa regeneração do osso interproximal. Concluiu-se que a eliminação da atividade da doença periodontal pode ser um benefício obtido na RTG sem a visualização da total regeneração óssea
Depending on the morphology of bone lesions guided tissue regeneration (GTR) is an option of treatment. This procedure aims at selecting specific cells, using a membrane for its proliferation in the injured area. However, complete regeneration of the defect may not be achieved, and in this case extinguish of the disease is the only result. The objective of the present study was to evaluate the clinical treatment of an interproximal two wall defect, using GTR technique. The patient GWS, 22 years old, attended to SIOMSÆ clinic of Periodontics, complaining of gingival bleeding on teeth 45 and 46. After clinical and radiographic examinations, was verified the presence of interproximal bone loss on those teeth with probing depth (PD) of 9mm and bleeding on probing (BOP). The treatment plan was prepared and a non-surgical periodontal treatment was adopted. This approach wasn´t able to eliminate the problem, GTR was performed in the area.Was performed an intrasulcular incision, followed by total detachment of a flap, debridement, chemical decontamination of the root, insertion of xenogenic bone graft and an absorbable membrane, flap repositioning, and suturing. The control was performed every 30 days, and after 12 months, the region presented absence of BOP, PD reduction and increased clinical attachment level. However it was not observed a complete regeneration of interproximal bone. It was concluded that the elimination of periodontal disease activity may be a benefit of GTR but without total bone regeneration