Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice
نویسندگان
چکیده
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 islet facilitating grafting and functionality. Stem cell aggregation provides physiological interactions between enhances the in situ concentration modulators inflammation immunity. We established hanging-drop culture adult human skin fibroblast-like spheroids, spheroid-derived (SphCs) were characterized. assessed potential SphCs improving functionality by cotransplantation with marginal mass allogeneic an experimental diabetic mouse model characterized secretome spectrometry-based proteomics. multipotent progenitors their coculture anti-CD3 stimulated splenocytes decreased CD4+ T proliferation skewed cytokine secretion through increase Th2/Th1 ratio profile. SphCs-conditioned media attenuated apoptosis induced challenge vitro importantly, intratesticular administration did not show tumorigenicity immune-deficient mice. Moreover, improved glycemic control when cotransplanted without pharmacological immunosuppression. SphCs' protein differed from its paired counterpart containing 70% up- downregulated proteins biological processes that overall positively influenced such cytoprotection, cellular stress, metabolism, survival. In summary, performance T1D model, Future research is warranted to identify SphCs-secreted factors responsible islets' endurance.
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ژورنال
عنوان ژورنال: Brazilian Journal of Medical and Biological Research
سال: 2023
ISSN: ['0100-879X', '1414-431X']
DOI: https://doi.org/10.1590/1414-431x2023e12611