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Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report

BACKGROUND: Upon orthognathic mandibular advancement surgery the adjacent soft tissues can displace the distal bone segment and increase the load on the temporomandibular joint causing loss of its integrity. Remodeling of the condyle and temporal fossa with destruction of condylar cartilage and subc...

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Autores principales: de Souza Tesch, Ricardo, Takamori, Esther Rieko, Menezes, Karla, Carias, Rosana Bizon Vieira, Dutra, Cláudio Leonardo Milione, de Freitas Aguiar, Marcelo, Torraca, Tânia Salgado de Sousa, Senegaglia, Alexandra Cristina, Rebelatto, Cármen Lúcia Kuniyoshi, Daga, Debora Regina, Brofman, Paulo Roberto Slud, Borojevic, Radovan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889586/
https://www.ncbi.nlm.nih.gov/pubmed/29625584
http://dx.doi.org/10.1186/s13287-018-0806-4
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author de Souza Tesch, Ricardo
Takamori, Esther Rieko
Menezes, Karla
Carias, Rosana Bizon Vieira
Dutra, Cláudio Leonardo Milione
de Freitas Aguiar, Marcelo
Torraca, Tânia Salgado de Sousa
Senegaglia, Alexandra Cristina
Rebelatto, Cármen Lúcia Kuniyoshi
Daga, Debora Regina
Brofman, Paulo Roberto Slud
Borojevic, Radovan
author_facet de Souza Tesch, Ricardo
Takamori, Esther Rieko
Menezes, Karla
Carias, Rosana Bizon Vieira
Dutra, Cláudio Leonardo Milione
de Freitas Aguiar, Marcelo
Torraca, Tânia Salgado de Sousa
Senegaglia, Alexandra Cristina
Rebelatto, Cármen Lúcia Kuniyoshi
Daga, Debora Regina
Brofman, Paulo Roberto Slud
Borojevic, Radovan
author_sort de Souza Tesch, Ricardo
collection PubMed
description BACKGROUND: Upon orthognathic mandibular advancement surgery the adjacent soft tissues can displace the distal bone segment and increase the load on the temporomandibular joint causing loss of its integrity. Remodeling of the condyle and temporal fossa with destruction of condylar cartilage and subchondral bone leads to postsurgical condylar resorption, with arthralgia and functional limitations. Patients with severe lesions are refractory to conservative treatments, leading to more invasive therapies that range from simple arthrocentesis to open surgery and prosthesis. Although aggressive and with a high risk for the patient, surgical invasive treatments are not always efficient in managing the degenerative lesions. METHODS: We propose a regenerative medicine approach using in-vitro expanded autologous cells from nasal septum applied to the first proof-of-concept patient. After the required quality controls, the cells were injected into each joint by arthrocentesis. Results were monitored by functional assays and image analysis using computed tomography. RESULTS: The cell injection fully reverted the condylar resorption, leading to functional and structural regeneration after 6 months. Computed tomography images showed new cortical bone formation filling the former cavity space, and a partial recovery of condylar and temporal bones. The superposition of the condyle models showed the regeneration of the bone defect, reconstructing the condyle original form. CONCLUSIONS: We propose a new treatment of condylar resorption subsequent to orthognathic surgery, presently treated only by alloplastic total joint replacement. We propose an intra-articular injection of autologous in-vitro expanded cells from the nasal septum. The proof-of-concept treatment of a selected patient that had no alternative therapeutic proposal has given promising results, reaching full regeneration of both the condylar cartilage and bone at 6 months after the therapy, which was fully maintained after 1 year. This first case is being followed by inclusion of new patients with a similar pathological profile to complete an ongoing stage I/II study. TRIAL REGISTRATION: This clinical trial is approved by the National Commission of Ethics in Medical Research (CONEP), Brazil, CAAE 12484813.0.0000.5245, and retrospectively registered in the Brazilian National Clinical Trials Registry and in the USA Clinical Trials Registry under the Universal Trial Number (UTN) U1111–1194-6997. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-0806-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-58895862018-04-10 Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report de Souza Tesch, Ricardo Takamori, Esther Rieko Menezes, Karla Carias, Rosana Bizon Vieira Dutra, Cláudio Leonardo Milione de Freitas Aguiar, Marcelo Torraca, Tânia Salgado de Sousa Senegaglia, Alexandra Cristina Rebelatto, Cármen Lúcia Kuniyoshi Daga, Debora Regina Brofman, Paulo Roberto Slud Borojevic, Radovan Stem Cell Res Ther Research BACKGROUND: Upon orthognathic mandibular advancement surgery the adjacent soft tissues can displace the distal bone segment and increase the load on the temporomandibular joint causing loss of its integrity. Remodeling of the condyle and temporal fossa with destruction of condylar cartilage and subchondral bone leads to postsurgical condylar resorption, with arthralgia and functional limitations. Patients with severe lesions are refractory to conservative treatments, leading to more invasive therapies that range from simple arthrocentesis to open surgery and prosthesis. Although aggressive and with a high risk for the patient, surgical invasive treatments are not always efficient in managing the degenerative lesions. METHODS: We propose a regenerative medicine approach using in-vitro expanded autologous cells from nasal septum applied to the first proof-of-concept patient. After the required quality controls, the cells were injected into each joint by arthrocentesis. Results were monitored by functional assays and image analysis using computed tomography. RESULTS: The cell injection fully reverted the condylar resorption, leading to functional and structural regeneration after 6 months. Computed tomography images showed new cortical bone formation filling the former cavity space, and a partial recovery of condylar and temporal bones. The superposition of the condyle models showed the regeneration of the bone defect, reconstructing the condyle original form. CONCLUSIONS: We propose a new treatment of condylar resorption subsequent to orthognathic surgery, presently treated only by alloplastic total joint replacement. We propose an intra-articular injection of autologous in-vitro expanded cells from the nasal septum. The proof-of-concept treatment of a selected patient that had no alternative therapeutic proposal has given promising results, reaching full regeneration of both the condylar cartilage and bone at 6 months after the therapy, which was fully maintained after 1 year. This first case is being followed by inclusion of new patients with a similar pathological profile to complete an ongoing stage I/II study. TRIAL REGISTRATION: This clinical trial is approved by the National Commission of Ethics in Medical Research (CONEP), Brazil, CAAE 12484813.0.0000.5245, and retrospectively registered in the Brazilian National Clinical Trials Registry and in the USA Clinical Trials Registry under the Universal Trial Number (UTN) U1111–1194-6997. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-0806-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-07 /pmc/articles/PMC5889586/ /pubmed/29625584 http://dx.doi.org/10.1186/s13287-018-0806-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
de Souza Tesch, Ricardo
Takamori, Esther Rieko
Menezes, Karla
Carias, Rosana Bizon Vieira
Dutra, Cláudio Leonardo Milione
de Freitas Aguiar, Marcelo
Torraca, Tânia Salgado de Sousa
Senegaglia, Alexandra Cristina
Rebelatto, Cármen Lúcia Kuniyoshi
Daga, Debora Regina
Brofman, Paulo Roberto Slud
Borojevic, Radovan
Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
title Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
title_full Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
title_fullStr Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
title_full_unstemmed Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
title_short Temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
title_sort temporomandibular joint regeneration: proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes, and the first human case report
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889586/
https://www.ncbi.nlm.nih.gov/pubmed/29625584
http://dx.doi.org/10.1186/s13287-018-0806-4
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