Protection of rat pancreatic islet function and viability by coculture with rat bone marrow-derived mesenchymal stem cells

Abstract

The maintenance of viable and functional islets is critical in successful pancreatic islet transplantation from cadaveric sources. During the isolation procedure, islets are exposed to a number of insults including ischemia, oxidative stress and cytokine injury that cause a reduction in the recovered viable islet mass. A novel approach was designed in which streptozotocin (STZ)-damaged rat pancreatic islets (rPIs) were indirectly cocultured with rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to maintain survival of the cultured rPIs. The results indicated that islets cocultured with rBM-MSCs secreted an increased level of insulin after 14 days, whereas non-cocultured islets gradually deteriorated and cell death occurred. The cocultivation of rBM-MSCs with islets and STZ-damaged islets showed the expression of IL6 and transforming growth factor-β1 in the culture medium, besides the expression of the antiapoptotic genes (Mapkapk2, Tnip1 and Bcl3), implying the cytoprotective, anti-inflammatory and antiapoptotic effects of rBM-SCs through paracrine actions.

Mesenchymal Stem Cells: Possibilities of New Treatment Options

“…It has been reported that cultured MSCs spontaneously secrete TGF b 1 and IL-6, but not IFN g , IL-5, or IL-10 (Boumaza et al 2009 ;Karaoz et al 2010b ) . By direct inhibition of lymphocyte apoptosis, IL-6 secretion might play a major role in the antiapoptotic function of MSCs (Xu et al 2007 ) The suppression of various immune functions through the release of immunosuppressive factors (e.g., TGF b 1) by MSCs demonstrated their antiapoptotic effects (Puissant et al 2005 ) In our experimental studies (unpublished data), not only IL-6, but also the proinfl ammatory cytokine TGF b 1 secretion was observed in the culture medium of rPI-SCs (Fig.…”

Stem Cell Therapies for Type I Diabetes

“…Since CTLA4Ig treatment has previously induced long-term survival of xenogeneic pancreatic islet grafts (Lenschow, Zeng et al 1992;Eventov-Friedman, Tchorsh et al 2006), it is possible that similar pre-conditioning treatments in recipients will allow for the acceptance of ESC-IPC grafts. An alternative strategy is the co-culture of ESC-IPC with bone marrow-derived mesenchymal stem cells, since co-culture of cells with bone marrow-derived mesenchymal stem cells induces the expression of protective molecules such as IL6 (in a paradoxically anti-inflammatory role) and TGF 1, an immunosuppressive cytokine, and anti-apoptotic genes like Mapkapk2, Tnip1 or Bcl3 (Karaoz, Genc et al 2010). Another interesting strategy to prevent immune rejection of pancreatic progenitors is their encapsulation in alginate capsules with pores that allow for the passage of nutrients and insulin, but not immune cells (Tuch, Hughes et al 2011).…”

Insulin producing cells established using non-integrated lentiviral vector harboring PDX1 gene

“…For osteogenic differentiation, third passage hADSCs were cultured in osteogenic medium containing DMEM, 10% FBS, 0.1 mol/L dexamethasone, 50 mol/L ascorbate-2-phosphate and 10 mmol/L glycerophosphate for two weeks. Cultured cells were stained with Alizarin Red to detect bone matrix in differentiated cells [3,14,37,38] .…”

“…Medium was changed twice a week. Cultured cells were stained with Oil Red O to detect lipid accumulation in differentiated cells [4,14,37,38] . For osteogenic differentiation, third passage hADSCs were cultured in osteogenic medium containing DMEM, 10% FBS, 0.1 mol/L dexamethasone, 50 mol/L ascorbate-2-phosphate and 10 mmol/L glycerophosphate for two weeks.…”