Nasal septum-derived chondroprogenitor cells control mandibular condylar resorption consequent to orthognathic surgery: a clinical trial

Author:

Tesch Ricardo de Souza1ORCID,Takamori Esther Rieko1,Menezes Karla2,Carias Rosana Bizon Vieira1,Rebelatto Carmen Lucia Kuniyoshi3,Senegaglia Alexandra Cristina3,Daga Debora Regina3,Fracaro Leticia3,Robert Anny Waloski4,Pinheiro Carlos Bruno Reis5,Aguiar Marcelo de Freitas6,Blanco Pablo Javier7,Zilves Eduardo Guerreiro7,Brofman Paulo Roberto Slud3,Borojevic Radovan1

Affiliation:

1. Regenerative Medicine Laboratory, Petrópolis Medical School/ UNIFASE, Avenida Barão do Rio Branco 1003, Centro , Petrópolis, RJ 25680-120 , Brazil

2. Institute of Biomedical Sciences, Federal University of Rio de Janeiro , Ave. Carlos Chagas Filho 373, Sala B1-011, Cidade Universitária, Ilha Do Fundão, Rio de Janeiro, RJ 21941-590 , Brazil

3. Core for Cell Technology, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná , Prado Velho, Curitiba, PR 80215-901 , Brazil

4. Stem Cells Basic Biology Laboratory, Carlos Chagas Institute – FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader , 3775, Curitiba, PR, 81350-010 , Brazil

5. Postgraduate Program in Exercise and Sport Sciences, State University of Rio de Janeiro, Rua São Francisco Xavier 524, Maracanã , Rio de Janeiro, RJ, 20550-013 , Brazil

6. Department of Specific Formation, School of Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Rua Dr. Silvio Henrique Braune , 22, Nova Friburgo, RJ, 28625-650 , Brazil

7. Department of Mathematical and Computational Models, National Laboratory for Scientific Computing, Avenida Getúlio Vargas , 333, Petrópolis, RJ, 25651-075 , Brazil

Abstract

Abstract Condylar resorption is an aggressive and disability form of temporomandibular joint (TMJ) degenerative disease, usually non-respondent to conservative or minimally invasive therapies and often leading to surgical intervention and prostheses implantation. This condition is also one of the most dreaded postoperative complications of orthognathic surgery, with severe cartilage erosion and loss of subchondral bone volume and mineral density, associated with a painful or not inflammatory processes. Because regenerative medicine has emerged as an alternative for orthopedic cases with advanced degenerative joint disease, we conducted a phase I/IIa clinical trial (U1111-1194-6997) to evaluate the safety and efficacy of autologous nasal septal chondroprogenitor cells. Ten participants underwent biopsy of the nasal septum cartilage during their orthognathic surgery. The harvested cells were cultured in vitro and analyzed for viability, presence of phenotype markers for mesenchymal stem and/or chondroprogenitor cells, and the potential to differentiate into chondrocytes, adipocytes, and osteoblasts. After the intra-articular injection of the cell therapy, clinical follow-up was performed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and computed tomography (CT) images. No serious adverse events related to the cell therapy injection were observed during the 12-month follow-up period. It was found that autologous chondroprogenitors reduced arthralgia, promoted stabilization of mandibular function and condylar volume, and regeneration of condylar tissues. This study demonstrates that chondroprogenitor cells from the nasal septum may be a promise strategy for the treatment of temporomandibular degenerative joint disease that do not respond to other conservative therapies.

Funder

Octacilio Gualberto Foundation

Rio de Janeiro State Research Support Foundation

Publisher

Oxford University Press (OUP)

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