Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes

二维和三维培养的脂肪组织来源干细胞对链脲佐菌素诱发的1型糖尿病小鼠的分泌组作用

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作者:Isabelle Dias, Daphne Pinheiro, Karina Ribeiro Silva, Ana Carolina Stumbo, Alessandra Thole, Erika Cortez, Laís de Carvalho, Simone Nunes Carvalho

Aims

To analyze therapeutic potential of the conditioned medium from adipose tissue-derived stem cells (ASC) cultivated in 2D (CM-2D) and 3D (CM-3D) models, in mice with Type 1 diabetes (T1D) induced by streptozotocin. Main

Methods

Viability andCD105 expression of 2D and 3D ASC were analyzed by flow cytometry. T1D was induced in mice by multiple injections of streptozocin. On the 28th and 29th days after the first injection of streptozocin, diabetic animals received CM-2D or CM-3D. Pancreatic, CM-2D, and CM-3D cytokines were analyzed by cytometric bead array (CBA) and insulin and PDX-1 were observed and quantified by immunohistochemistry. Apoptosis-related proteins were quantified by Western Blotting. Key findings: ASC in three-dimensional culture released increased levels of IL-6 and IL-2, while IL-4 was decreased. CM-2D induced pancreatic PDX-1 expression and was able to reduce glycemia in diabetic mice one week after injections but not CM-3D. On the other hand, CM-2D and CM-3D were not able to reverse apoptosis of pancreatic cells in diabetic mice nor to increase insulin expression. Significance: Together, these

Significance

Together, these results demonstrate that the 3D cell culture secretome was not able to improve diabetes type 1 symptoms at the times observed, while 2D cell secretome improved glycemic levels in T1D mice.

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