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(Referência obtida automaticamente do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice

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Autor(es):
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L. Andreone ; A.F. dos Santos [2] ; R.A.M. Wailemann [3] ; L.F. Terra [4] ; V.M. Gomes [5] ; J. Macedo da Silva [6] ; L. Rosa-Fernandes [7] ; M.C. Sogayar ; G. Palmisano [9] ; L. Labriola [10] ; M.J. Perone
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: Brazilian Journal of Medical and Biological Research; v. 56, 2023-09-22.
Resumo

Islet transplantation represents a therapeutic option for type 1 diabetes (T1D). Long-term viability of transplanted islets requires improvement. Mesenchymal stromal cells (MSCs) have been proposed as adjuvants for islet transplantation facilitating grafting and functionality. Stem cell aggregation provides physiological interactions between cells and enhances the in situ concentration of modulators of inflammation and immunity. We established a hanging-drop culture of adult human skin fibroblast-like cells as spheroids, and skin spheroid-derived cells (SphCs) were characterized. We assessed the potential of SphCs in improving islet functionality by cotransplantation with a marginal mass of allogeneic islets in an experimental diabetic mouse model and characterized the secretome of SphCs by mass spectrometry-based proteomics. SphCs were characterized as multipotent progenitors and their coculture with anti-CD3 stimulated mouse splenocytes decreased CD4+ T cell proliferation with skewed cytokine secretion through an increase in the Th2/Th1 ratio profile. SphCs-conditioned media attenuated apoptosis of islets induced by cytokine challenge in vitro and importantly, intratesticular SphCs administration did not show tumorigenicity in immune-deficient mice. Moreover, SphCs improved glycemic control when cotransplanted with a marginal mass of allogeneic islets in a diabetic mouse model without pharmacological immunosuppression. SphCs' protein secretome differed from its paired skin fibroblast-like counterpart in containing 70% of up- and downregulated proteins and biological processes that overall positively influenced islets such as cytoprotection, cellular stress, metabolism, and survival. In summary, SphCs improved the performance of transplanted allogeneic islets in an experimental T1D model, without pharmacological immunosuppression. Future research is warranted to identify SphCs-secreted factors responsible for islets' endurance. (AU)

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
Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 12/16785-4 - Estudo das vias de sinalização mediadoras dos efeitos citotóxicos da terapia fotodinâmica em células de tumores mamários humanos
Beneficiário:Ancély Ferreira dos Santos
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/07029-4 - Estudo do papel da proteína HSP27/25 na citoproteção de células beta pancreáticas induzida por prolactina
Beneficiário:Leticia Labriola
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/50680-5 - Fotossensibilização nas ciências da vida
Beneficiário:Mauricio da Silva Baptista
Modalidade de apoio: Auxílio à Pesquisa - Temático