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Differential stress responses of immunoisolated human islets embedded in pancreatic extracellular matrix under static and free-fall dynamic conditions

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Autor(es):
Borges-Silva, Isaura ; Mantovani, Marluce da Cunha ; Danh Anh Luu, Minh ; Gorter, Alan ; Borghuis, Theo ; Gasaly, Naschla ; Cleide Sogayar, Mari ; de Vos, Paul ; Trombetta-Lima, Marina
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF TISSUE ENGINEERING; v. 16, p. 21-pg., 2025-01-01.
Resumo

Pancreatic islet transplantation offers great promise for the treatment of type 1 diabetes, yet the functional decline of islets after isolation remains a major obstacle. Increasing evidence highlights the endoplasmic reticulum (ER) as a critical regulator of islet cell survival under stress. We explored how ex vivo culture conditions affect encapsulated islet resilience under ER-stress. Two conditions were assessed: (i) incorporation of decellularized porcine pancreatic extracellular matrix (ECM) into alginate microcapsules, and (ii) free-fall dynamic pre-conditioning culture. Human islets were encapsulated in alginate with or without ECM, cultured under static or dynamic conditions, and exposed to acute ER-stress followed or not by a recovery period. Dynamic culture preserved viability and enhanced glucose responsiveness. ECM-containing capsules showed reduced inflammatory marker expression, while encapsulation in alginate-only capsules led to more pronounced changes associated with ECM remodeling. Under ER-stress, the dynamic culture, especially combined with ECM, maintained cell function and reduced cell death. Gene profiles indicated improved stress adaptation and ECM remodeling. These results highlight ECM enrichment and dynamic culture as good strategies to maintain islet survival and functionality. (AU)

Processo FAPESP: 19/21935-4 - Caracterização do transcritoma de células-tronco embrionárias durante sua diferenciação em células produtoras de insulina na ausência e presença de fatores peptídicos de crescimento/diferenciação
Beneficiário:Isaura Beatriz Borges Silva
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 21/12497-3 - Avaliação de um polímero de pectina e da prolactina recombinante humana na melhoria da viabilidade e funcionalidade de ilhotas pancreáticas microencapsuladas
Beneficiário:Isaura Beatriz Borges Silva
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 16/05311-2 - Medicina regenerativa visando à terapia de doenças crônico-degenerativas (câncer e diabetes)
Beneficiário:Mari Cleide Sogayar
Modalidade de apoio: Auxílio à Pesquisa - Temático