Effects of Human Placental Amnion Derived Mesenchymal Stem Cells on Proliferation and Apoptosis Mechanisms in Chronic Kidney Disease in the Rat

BACKGROUND AND OBJECTIVES: The feature of chronic kidney failure (CKF) is loss of kidney functions due to erosion of healthy tissue and fibrosis. Recent studies showed that Mesenchymal stem cells (MSCs) differentiated into tubular epithelial cells thus renal function and structures renewed. Furthermore, MSCs protect renal function in CKF. Therefore, we aimed to investigate whether human amnion-derived mesenchymal stem cells (hAMSCs) can repair fibrosis and determine the effects on proliferation and apoptosis mechanisms in chronic kidney failure. METHODS AND RESULTS: In this study, rat model of CKF was constituted by applying Aristolochic acid (AA). hAMSCs were isolated from term placenta amnion membrane and transplanted into tail vein of rats. At the end of 30 days and 60 days of recovery period, we examined expressions of PCNA, p57 and Parp-1 by western blotting. Immunoreactivity of PCNA, Ki67, IL-6 and Collagen type I were detected by immunohistochemistry. Besides, apoptosis was detected by TUNEL. Serum creatinine and urea were measured. Expressions of PCNA and Ki67 increased in hAMSC groups compared with AA group. Furthermore, expressions of PARP-1 apoptosis marker and p57 cell cycle inhibitory protein increased in AA group significantly according to control, hAMSC groups and sham groups. IL-6 proinflammatory cytokine increased in AA group significantly according to control, hAMSCs groups and sham groups. Expressions of Collagen type I protein reduced in hAMSCs groups compared to AA group. After hAMSC treatment, serum creatinine and urea levels significantly decreased compared to AA group. After injection of hAMSC to rats, Masson’s Trichrome and Sirius Red staining showed fibrosis reduction in kidney. CONCLUSIONS: According to our results hAMSCs can be ameliorate renal failure.

Increased peripheral CD4[+] CD25[high] Treg in prostate cancer patients is correlated with PSA

To determine peripheral frequencies of CD4[+]CD25[high]Foxp3[+] regulatory T cells [Treg] in prostate cancer [PCa] patients, and to investigate if there is a correlation between peripheral Treg and total serum prostate specific antigen [PSA] levels in PCa patients. Peripheral blood mononuclear cells from 56 subjects undergoing diagnostic prostate biopsies PSA >/= 2.5ng/ml were analyzed for Treg numbers. Association between the peripheral Treg and serum PSA values was first determined in the entire population, including people with no prostate pathology, PCa, and benign prostate hyperplasia [BPH] patients, and second, in 9 PCa patients before and after curative prostatectomy. In this study, the 3 groups were compared. This project was performed in the Akdeniz University Immunology laboratory, and the Urology outpatient clinic, Antalya, Turkey from December 2008 to January 2010. Peripheral Treg frequencies were significantly increased in the PCa patients [n=19, 3.23 +/- 1.59] compared with BPH patients [n=27, 1.66 +/- 0.80], and healthy subjects [n=10, 1.08 +/- 0.43] [p=0.007]. The percentage of Treg in BPH patients was also significantly higher than healthy subjects [p=0.007]. The increase of Treg in BPH and PCa patients was positively correlated with total serum PSA levels [r=0.75; p=0.007]. Peripheral Treg densities are correlated with PSA in BPH and PCa patients, suggesting that PSA may have a role in Treg induction and/or maintenance