The Antidiabetic Effect of MSCs is not Impaired by Insulin Prophylaxis and is not Improved by a Second Dose of Cells

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dc.contributor.authorEzquer, Fernando
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorSimon, Valeska
dc.contributor.authorConget, Paulette
dc.date.accessioned2016-12-07T17:04:11Z
dc.date.available2016-12-07T17:04:11Z
dc.date.issued2011
dc.description.abstractType 1 diabetes mellitus (T1D) is due to autoimmune destruction of pancreatic beta-cells. Previously, we have shown that intravenously administered bone marrow-derived multipotent mesenchymal stromal cells (MSCs) allows pancreatic islet recovery, improves insulin secretion and reverts hyperglycemia in low doses streptozotocin (STZ)-induced diabetic mice. Here we evaluate whether insulin prophylaxis and the administration of a second dose of cells affect the antidiabetic therapeutic effect of MSC transplantation. Insulitis and subsequent elimination of pancreatic beta-cells was promoted in C57BL/6 mice by the injection of 40 mg/kg/day STZ for five days. Twenty-four days later, diabetic mice were distributed into experimental groups according to if they received or not insulin and/or one or two doses of healthy donor-derived MSCs. Three and half months later: glycemia, pancreatic islets number, insulinemia, glycated hemoglobin level and glucose tolerance were determined in animals that did not received exogenous insulin for the last 1.5 months. Also, we characterized MSCs isolated from mice healthy or diabetic. The therapeutic effect of MSC transplantation was observed in diabetic mice that received or not insulin prophylaxis. Improvements were similar irrespective if they received one or two doses of cells. Compared to MSCs from healthy mice, MSCs from diabetic mice had the same proliferation and adipogenic potentials, but were less abundant, with altered immunophenotype and no osteogenic potential. Our preclinical results should be taken into account when designing phase II clinical trials aimed to evaluate MSC transplantation in patients with T1D. Cells should be isolated form healthy donor, insulin prophylaxis could be maintained and a second dose, after an elapse of two months, appears unnecessary in the medium-term.
dc.identifier.citationPLOS ONE, 2011, vol. 6, n° 1, Número de artículo: e16566
dc.identifier.urihttp://hdl.handle.net/11447/874
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0016566
dc.language.isoen_US
dc.subjectMesenchymal stem-cells
dc.subjectHepatocyte growth-factor
dc.subjectVersus-host-disease
dc.subjectBone-marrow-cells
dc.subjectStromal cells
dc.subjectIslet transplantation
dc.subjectProgenitor cells
dc.subjectDiabetic mice
dc.subjectIn-vitro
dc.subjectTissue-repair
dc.titleThe Antidiabetic Effect of MSCs is not Impaired by Insulin Prophylaxis and is not Improved by a Second Dose of Cells
dc.typeArtículo

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