Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury

BACKGROUND AND OBJECTIVES: In regenerative medicine, mesenchymal stem cells derived from adipose tissues (Ad-MSCs) are a very attractive target to treat many diseases. In relation to nephrology, the aim of the current study is to investigate the effects of Ad-MSCs for the amelioration of acute kidney injury and to explore the mechanism of renal parenchymal changes in response to allogeneic transplantation of Ad-MSCs. METHODS AND RESULTS: The nephrotoxicity was induced by cisplatin (CP) in balb/c mice according to RIFLE Class and AKIN Stage 3. PCR, qRT-PCR and fluorescent labeled cells infusion, histopathology, immunohistochemistry, functional analyses were used for genes and proteins expressions data acquisition respectively. We demonstrated that single intravenous infusion of 2.5×107/kg mAd-MSCs in mice pre-injected with CP recruited to the kidney, restored the renal structure, and function, which resulted in progressive survival of mice. The renal tissue morphology was recovered in terms of diminished necrosis or epithelial cells damage, protein casts formation, infiltration of inflammatory cells, tubular dilatation, and restoration of brush border protein; Megalin and decreased Kim-1 expressions in mAd-MSCs transplanted mice. Significant reduction in serum creatinine with slashed urea and urinary protein levels were observed. Anti-BrdU staining displayed enhanced tubular cells proliferation. Predominantly, downgrade expressions of TNF-α and TGF-β1 were observed post seven days in mAd-MSCs transplanted mice. CONCLUSIONS: Ad-MSCs exerts pro-proliferative, anti-inflammatory, and anti-fibrotic effects. Ad-MSCs transplantation without any chemical or genetic manipulation can provide the evidence of therapeutic strategy for the origin of regeneration and overall an improved survival of the system in functionally deprived failed kidneys.

Bilirubin Pigments in the first Meconium of newborn infants

To determine the pattern of excretion of total bilirubin IXa and IXb in the first meconium of newborn infants. First two newborns of varying gestational age were selected every week through random sampling from the neonatal unit. Of the 41 newborn infants selected 8 expired before meconium passage, hence the results are from 33 newborns. Meconium was collected and stored at -20°C, protected by aluminium foil. Samples were defrosted, vortex mixed with equal amount of dimethyl-sulfoxide, centrifuged, and analyzed by HPLC. Unconjugated Bilirubin-IXa and -IXb were identified and quantitative estimation of Bilirubin-IXa done. Bilirubin-IXb was greater than 50% of the total, in the first meconium of the newborn. Amount of bilirubin excreted in meconium was 29.2 - 90.8 mg [0.051 - 0.155 mmol] per sample of meconium passed. Amount was 9.7 mg/ Kg of body weight in term newborn and 12 mg / kg in preterm.The amount of bilirubin -IXb decreases and bilirubin-IXa increases with increasing gestational age. Newborns with birth asphyxia [BA] had significantly greater quantity of bilirubin in meconium, compared to infants without BA [JPMA 55:188;2005].

Impact of cyclosporin immunosuppression on serum magnesium and its fractional excretion in renal transplant recipients

To evaluate the effect of cyclosporine [CSA] on serum magnesium and its fractional excretion in renal transplant recipients. A cross sectional comparative study on 50 live related renal transplant recipients on CSA therapy with serum creatinine <2.0 mg/dl and 30 healthy controls. Serum creatinine, magnesium and its fractional excretion and CSA levels were monitored. Patients were followed at 6 months. The mean serum creatinine in patients was 1.41 +/- 0.42 mg/dl, cyclosporine 210 +/- 66 ng/ml at a dose of 4.8 +/- 1.4 mg/kg/day. The serum magnesium was 1.77 +/- 0.32mg/dl vs 1.98 +/- 0.17mg/dl in healthy controls [p<0.05].Fractional excretion was 5.05 +/- 2.53% in patients vs 2.8 +/- 1.05% in controls [p<0.05]. No correlation was found between CSA levels [100-400 ng/ml] and serum magnesium [r = 0.053] or FEMg% [r = 0.215]. Of the 50 recipients 27 [54%] had FEMg% in the control range. At 6 months follow up no difference in CSA levels was found between recipients with FEMg% in the normal range vs those with FEMg >5%. However, serum creatinine increased from 1.42 +/- 0.30 mg/dl to 1.68 +/- 0.82mg/dl [p< 0.05]. CSA therapy lowers serum magnesium as compared to healthy controls and there is marked increase in FEMg% in 50% of the patients. Patients with FEMg >5% developed renal function deterioration. FEMg% can thus be a good follow up marker of CSA chronic toxicity in stable transplant recipients