The Antidiabetic Effect of Mesenchymal Stem Cells Is Unrelated to Their Transdifferentiation Potential But to Their Capability to Restore Th1/Th2 Balance and to Modify the Pancreatic Microenvironment

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dc.contributor.authorEzquer, Fernando
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorContador, David
dc.contributor.authorRicca, Micaela
dc.contributor.authorSimón, Valeska
dc.contributor.authorConget, Paulette
dc.date.accessioned2021-09-30T22:16:54Z
dc.date.available2021-09-30T22:16:54Z
dc.date.issued2012
dc.description.abstractType 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from cell-mediated autoimmune destruction of insulin-producing cells. In T1DM animal models, it has been shown that the systemic administration of multipotent mesenchymal stromal cells, also referred as to mesenchymal stem cells (MSCs), results in the regeneration of pancreatic islets. Mechanisms underlying this effect are still poorly understood. Our aims were to assess whether donor MSCs (a) differentiate into pancreatic b-cells and (b) modify systemic and pancreatic pathophysiologic markers of T1DM. After the intravenous administration of 5 3 105 syngeneic MSCs, we observed that mice with T1DM reverted their hyperglycemia and presented no donor-derived insulin-producing cells. In contrast, 7 and 65 days post-transplantation, MSCs were engrafted into secondary lymphoid organs. This correlated with a systemic and local reduction in the abundance of autoaggressive T cells together with an increase in regulatory T cells. Additionally, in the pancreas of mice with T1DM treated with MSCs, we observed a cytokine profile shift from proinflammatory to antinflammatory. MSC transplantation did not reduce pancreatic cell apoptosis but recovered local expression and increased the circulating levels of epidermal growth factor, a pancreatic trophic factor. Therefore, the antidiabetic effect of MSCs intravenously administered is unrelated to their transdifferentiation potential but to their capability to restore the balance between Th1 and Th2 immunological responses along with the modification of the pancreatic microenvironment. Our data should be taken into account when designing clinical trials aimed to evaluate MSC transplantation in patients with T1DM since the presence of endogenous precursors seems to be critical in order to restore glycemic control.es
dc.identifier.citationSTEM CELLS, 2012;30:1664–1674es
dc.identifier.urihttps://doi.org/10.1002/stem.1132es
dc.identifier.urihttp://hdl.handle.net/11447/4747
dc.language.isoenes
dc.subjectRegenerative medicinees
dc.subjectType 1 diabetes mellituses
dc.subjectMultipotent mesenchymal stromal cellses
dc.subjectMesenchymal stem cellses
dc.subjectPathophysiological markerses
dc.titleThe Antidiabetic Effect of Mesenchymal Stem Cells Is Unrelated to Their Transdifferentiation Potential But to Their Capability to Restore Th1/Th2 Balance and to Modify the Pancreatic Microenvironmentes
dc.typeArticlees

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