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.
Objective: The aim was to evaluate the effects of diagnostic performance of diffusionweighted (DW) MRI in the assessment of acute impairment of transplanted kidneys. Methods: From January 2009 to January 2010, 49 patients with stable renal allograft function (Group 1) and 21 patients with acute graft impairment (Group 2) were included in the study. All patients were evaluated with coronal T 2 weighted (T 2 W) and DW MRI of the kidney. Patients in Group 2 underwent graft biopsy to determine the underlying histopathological aetiology. Apparent diffusion coefficient (ADC) was calculated and the kidneys were studied for any areas of diffusion restriction. Two radiologists, who were blinded to the results of histopathology, independently interpreted the T 2 W and DW images. Results: The histopathological diagnosis ofGroup 2 (21 patients) was acute cellular rejection (ACR) in 10, acute tubular necrosis (ATN) in 7 and immunosuppressive toxicity in 4 patients. ADC values in Group 1 were significantly higher compared with Group 2 (p,0.001), patients with ACR (p,0.001), patients with ATN (p,0.001) and patients with drug toxicity (p,0.001). Using 2610 23 mm 2 s 21 as a cut-off, there was no overlap between the ADC values of patients with normal graft function and those with ATN. Both ACR and ATN had a low ADC value, but on the ADC map the kidney in cases of ATN appears heterogeneous with a characteristic mosaic pattern resembling the Tiger skin. There was no significant T 2 W morphological difference between the two groups. Conclusion: These results show how DW MRI is a promising new technique for the diagnosis of acute renal transplant dysfunction.
Background/Aim: Transforming growth factor-β1 (TGF-β1) is involved in the pathogenesis of chronic allograft nephropathy after kidney transplantation. The aim of the study was to evaluate the effect of the angiotensin receptor blocker losartan on TGF-β1 plasma levels and proteinuria in hypertensive transplant recipients. Methods: A total of 162 transplant recipients were included in the study. The patients were randomized into 3 groups: group 1 received losartan; group II received an angiotensin-converting enzyme inhibitor (captopril), and group III received a calcium channel blocker (amlodipine). All the parameters were recorded at the time of therapy initiation and at 1, 4 and 12 weeks and 12 months thereafter. Graft biopsy before the start and at the end of the study was done to evaluate histopathological progression. Results: Blood pressure was controlled in the 3 groups; however, the need for other antihypertensive agents was significant in groups I and II. Treatment with losartan significantly decreased the plasma level of TGF-β1, 24-hour urinary protein and serum uric acid (p < 0.05). No significant changes were seen in the hemoglobin or serum potassium levels. The rate of histopathological progression was significantly lower in the losartan group. No patient was discharged from the study due to side effects. Conclusions: After transplantation all drugs were able to control blood pressure with good safety and tolerability. The study demonstrates that ARB significantly decreases the plasma levels of TGF-β1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.
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