Harvesting, expansion and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and 3 non-diabetic donors. After 3 days in culture, adherent MSCs were expanded for 2 passages. At passage 3, differentiation was carried out in a 3-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in-vitro by flow cytometry, immunolabelling, Rt-PCR and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell-clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ~5–10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin and c-peptide were co-expressed. Nanogold immunolabelling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPCs-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and non-diabetic human subjects could be differentiated without genetic manipulation to form IPCs which, when transplanted, could maintain euglycaemia in diabetic mice for 3 months. Optimization of the culture conditions are required to improve the yield of IPCs and their functional performance.
Kimura disease (KD) is a chronic inflammatory disorder with angiolymphatic proliferation, usually affecting young men of Asian race but is rare in other races. The etiology of KD is still unknown. It is often accompanied by nephrotic syndrome. Herein, we present an atypical manifestation of Kimura disease occurring in a Caucasian man with steroid-responsive early membranous glomerulonephritis. Kimura disease can present atypically in a middle-aged Caucasian man with secondary steroid-responsive nephrotic syndrome. Steroid, endoxan, and MMF can be used safely and successfully in such situation. The diagnosis of KD can be difficult and misleading, and patients with this disease are often evaluated using avoidable procedures by just not being aware of KD.
Multidetector row spiral CT with contrast medium can provide accurate information regarding the anatomy of the urinary tract and vasculature of the kidney. Moreover, it can detect renal and vascular abnormalities that might be potentially significant for safe renal donation. In addition, it can accurately demonstrate selective GFR of each kidney. Therefore, we recommend spiral CT with contrast material as a single radiological diagnostic modality for the assessment of potential live kidney donors.
A total of 400 male renal transplant recipients (RTR) were investigated. Data on medical, sexual history, clinical examination and laboratory variables were collected. The severity of erectile dysfunction (ED) was assessed using the International Index of Erectile Function questionnaire. Univariate and multivariate logistic regression analyses were used to determine prognostic variables, which have independent impact on erectile function. ED was detected in 35.8% of the whole group. Current erectile function as compared to pretransplant status was improved, deteriorated or remained static in 44, 12.5 and 43.5% of the evaluated transplant recipients, respectively. After logistic regression analysis, age, hemoglobin level and presence of DM and/or peripheral neuropathy had significant and independent negative impact on erectile function. We concluded that renal transplantation has varying effects on erectile function. ED is highly prevalent among RTR and its pathogenesis is multifactorial.
Introduction. Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs) to form insulin-producing cells (IPCs). We compared the relative efficiency of three differentiation protocols. Methods. Human bone marrow-derived MSCs (HBM-MSCs) were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), and β-mercaptoethanol-based (three-step protocol). At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. Results. By immunolabeling, the proportion of generated IPCs was modest (≃3%) in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. Conclusion. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.
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