Abstract Bone marrow–mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in ...the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group). Compared to the islet group, islet + MSCs had a lower expression of inflammatory markers, such as, tumor necrosis factor– α (13.40 ± 0.57 vs. 9.90 ± 0.12, P = .01), monocyte chemoattractant protein 1 (51.30 ± 6.80 vs. 9.00 ± 1.80, P = .01), and interleukin 1β (IL-1β) (16.2 ± 1.65 vs. 6.80 ± 1.00, P = .04). Comparing the expression of immune tolerance markers, it is noted that animals receiving the co-transplantation showed a significantly higher expression than the islet group of IL-4 (25.60 ± 1.96 vs. 2.80 ± 0.20, P = .004), IL-10 (188.40 ± 4.60 vs. 4.55 ± 0.12, P = .0001), and forkhead box P3 (34.20 ± 1.3 vs. 1.30 ± 0.2, P = .004), respectively. These results suggest an immunomodulatory action of BM-MSC in islet xenotransplantation showing that these stem cells have the potential to mitigate the early losses of grafts, due to the regulation of the inflammatory process of transplantation.
Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after transplantation, important for the correction of conditions such as metabolic storage disorders, can occur but with poor ...efficiency. Substantial improvements in engraftment will be required in order to derive a clinical benefit from MSC transplantation. Chemokines are the most important factors controlling cellular migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in promoting the migration of cells to the bone marrow, via its specific receptor CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its role in mediating migration to bone marrow. We show that CXCR4, although present at the surface of a small subset of MSCs, is important for mediating specific migration of these cells to bone marrow. (Blood. 2004; 104:2643-2645)
Abstract Background Mesenchymal stem cells (MSCs) from human umbilical cord vein have great potential for use in cell therapy because of their ease of isolation, expansion, and differentiation, in ...addition to their relative acceptance from the ethical point of view. Obtaining the umbilical cord at birth does not present any risk to either mother or child. Objective To isolate and promote in vitro expansion and differentiation of MSCs from human umbilical cord vein into cells with a pancreatic endocrine phenotype. Methods Mesenchymal stem cells obtained from human umbilical cord vein via collagenase digestion were characterized at cytochemistry and fluorescent-activated cell sorting, and expanded in vitro. Differentiation of MSCs into an endocrine phenotype was induced using high-glucose (23 mmol/L) medium containing nicotinamide, exendin-4, and 2-mercaptoethanol. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was analyzed using immunofluorescence. Results Cells isolated from the umbilical cord vein were MSCs as confirmed at cytochemistry and fluorescent-activated cell sorting. Expression of somatostatin, glucagon, and pancreatic and duodenal homeobox 1 by differentiated cells was demonstrated using immunofluorescence. Insulin was not expressed. Conclusions The MSC differentiation protocol used in the present study induced expression of some endocrine markers. Insulin was not produced by these cells, probably because of incomplete induction of differentiation.
Abstract Background Mesenchymal stem cells (MSCs) are an attractive source for generation of cells with β-cell properties. Previous studies have demonstrated the ability of prolactin to induce an ...increase in β-cell mass and maturation, which suggests beneficial effects of its use in MSC differentiation protocols. Objective To evaluate the expression of endocrine differentiation markers in rat MSCs treated in vitro with prolactin. Methods Mesenchymal stem cells from bone marrow of Wistar rats were isolated, expanded, and characterized. Differentiation of MSCs was induced in medium containing 23 mmol/L of glucose, and nicotinamide, 2-mercaptoethanol, and exendin-4, in the presence or absence of 500 ng/mL of rat recombinant prolactin. Expression of endocrine markers and prolactin receptor genes was evaluated using real-time polymerase chain reaction, and compared between culture stages and presence vs absence of prolactin in the culture medium. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was also evaluated at immunofluorescence microscopy. Results Isolated cells were mostly MSCs, as confirmed at fluorescent-activated cell sorting and cytochemistry. Pax6, Ngn-3, Isl1, NeuroD1, Nkx2.2 , and Nkx6.1 exhibited varied expression during culture stages. The long form of the prolactin receptor messenger RNA was induced in prolactin-treated cultures ( P < .05). The somatostatin gene was induced in early stages of differentiation ( P < .05), and its expression was induced by prolactin, as confirmed using immunofluorescence. Conclusion Culture of rat bone marrow MSCs in differentiation medium induces expression of pancreatic endocrine-specific genes, and somatostatin and prolactin receptor expression was also induced by prolactin.
The relationship between malnutrition in hemodialysis (HD) patients with a chronic inflammatory condition and the expression levels of leukocyte integrins and their adhesiveness to fibronectin was ...investigated.
Subjective global assessment, albumin and body mass index were used as nutritional markers to group malnourished (MP) and eutrophic (EP) patients. C-reactive protein was used as an inflammation marker. LFA-1, VLA-4 and VLA-5 expression levels on circulating leukocytes before and after HD were flow cytometrically measured; and their adhesiveness, through immobilized fibronectin.
MPs showed significantly higher VLA-5 expression on granulocytes, when compared with healthy individuals (HPs) as controls (13.7% +/- 2.3% vs. 5.0% +/- 1.1%; p=0.005), particularly after HD (25.8% +/- 4.1%; p<0.001). They also presented a significantly lower ability to adhere to fibronectin when compared with EPs, before HD (48.8% +/- 1.5% vs. 62.3% +/- 0.7%; p<0.001) and after HD (50.6% +/- 1.2% vs. 65.7% +/- 1.4%; p<0.0001). Increased numbers of circulating immature neutrophils were observed only in MPs.
Although presenting higher VLA-5 expression, malnutrition in HD patients is associated with impairment of the adhesive capacity of circulating leukocytes, particularly younger neutrophils, which may contribute to the chronic inflammatory status of these patients.
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