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Cell sheet produced from periodontal ligament stem cells activated by PAR1 improves osteogenic differentiation

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Autor(es):
Gasparoni, Leticia Miquelitto ; Alves, Tomaz ; de Franca, Bruno Nunes ; Balzarini, Danilo ; Albuquerque-Souza, Emmanuel ; Pedroni, Ana Clara Fagundes ; da Silva Rovai, Emanuel ; Mendoza, Aldrin Huaman ; Sipert, Carla Renata ; Holzhausen, Marinella
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: BRAZILIAN ORAL RESEARCH; v. 38, p. 16-pg., 2024-01-01.
Resumo

Periodontal regeneration is a challenge, and tissue engineering based on periodontal ligament stem cells (PDLSCs) has been shown to be a promising alternative to this process. However, the need for scaffolds has limited the therapeutic use of PDLSCs. In this context, scaffold-free tissue engineering using the cell sheet (CS) technique has been developed as an alternative approach to improve tissue regeneration. Previously, we showed that Protease-activated receptor-1 (PAR1) can regulate PDLSCs. Herein, we evaluate whether PAR1 influences osteogenesis in CSs produced from PDLSCs, without the use of scaffolds. PDLSCs were isolated and immunophenotyped. Then, CSs were obtained by supplementing the culture medium with ascorbic acid (50 mu g/mL), and PAR1 was activated through its agonist peptide (100 nM). Scaffold-free 3D CSs were successfully produced from PDLSCs, and they showed higher proliferation potential than isolated PDLSCs. Also, PAR1 activation decreased senescence and improved osteogenic differentiation of CSs by increasing mineralized nodule deposition and alkaline phosphatase concentration; PAR1 also modulated osteogenic markers at the gene and protein levels. We further demonstrated that this effect was regulated by Wnt, TGF-beta I, MEK, p38 MAPK, and FGF/VEGF signaling pathways in PDLSCs (p < 0.05%). Overall, PAR1 activation increased osteogenic activity in CSs, emerging as a promising scaffold-free therapeutic approach for periodontal regeneration. (AU)

Processo FAPESP: 18/13818-5 - Efeito da ativação do Receptor Ativado por Protease do tipo 1 (PAR1) sobre a atividade osteogênica em membranas de células-tronco do ligamento periodontal humano. ensaio in vivo
Beneficiário:Tomaz Alves da Silva Neto
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 17/23158-0 - Efeito da ativação do receptor ativado por protease do tipo 1 (par1) sobre a atividade osteogênica em membranas de células-tronco do ligamento periodontal humano
Beneficiário:Marinella Holzhausen Caldeira
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/15740-3 - Efeito osteogênico da ativação do receptor par1 em membranas de células-tronco sintetizadas a partir de células do ligamento periodontal
Beneficiário:Danilo Andrés Balzarini
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica