Dina Sabry

The present study was conducted to compare between the therapeutic efficacies of human amniotic membrane-derived stem cells (hAM-MSCs) vs. adipose tissue derived stem cells (AD-MSCs) in cyclophosphamide (CTX)-induced ovarian failure in rats. Forty-eight adult female rats were included in the study; 10 rats were used as control group. Thirty-eight rats were injected with CTX to induce ovarian failure and divided into four groups: ovarian failure (IOF) (IOF group), IOF + phosphate buffer saline (PBS group), IOF + hAM-MSCs group and IOF + AD-MSCs group. Serum levels of FSH and estradiol (E2) were assessed. Histopathological examination of the ovarian tissues was performed and quantitative gene expressions of Oct-4, Stra8 and integrin beta-1 genes were conducted by quantitative real time PCR. Results showed that IOF and IOF + PBS rat groups exhibited decreased ovarian follicles, increased interstitial fibrosis with significant decrease of serum E2, significant increase serum FSH level and significant down-regulation of Stra8 and integrin beta-1. In hAM-MSCs and AD-MSCs rat groups, there were increased follicles and corpora with evident the presence of oocytes, significant increase in serum E2, significant decrease in serum FSH levels (in hAM-MSCs treated group only) and significant up-regulation of the three studied genes with higher levels in hAM-MSCs treated rats group when compared to AD-MSCs treated rats group. In Conclusion, administration of either hAM-derived MSCs or AD-MSCs exerts a significant therapeutic efficacy in chemotherapy induced ovarian insult in rats. hAM-MSCs exert higher therapeutic efficacy as compared to AD-MSCs.

AIMS: The study aimed to investigate the quantitative expression of NANOG, p38 α , NCF2, ELF and TGF-β genes in patients with colorectal adenocarcinoma, adenoma and normal colonic tissue and their correlation with SIRT-1 protein level expression.

METHOD: This study enrolled one hundred sixty seven patients; group A: 87 patients with colonoscopic findings of no adenoma or adenocarcinoma and group B: 80 patients with colorectal mass. Consecutive colonoscopic examinations were conducted, and tissue samples were taken from the colonic lesions/masses. Total RNA was isolated and mRNA expression level of NANOG, mitogen activated p38α , Neutrophil Cytosol Factor 2 (NCF2), Embryonic Liver Fodrin (ELF) and Transforming Growth Factor Beta (TGF-β) genes were quantified by qRT-PCR. Sirt-1 protein expression level was assessed by quantitative western blot.

RESULTS: There were significantly high level of mRNA transcripts expression of the genes studied in patients with adenocarcinoma and adenoma compared with normal tissue (P value < 0.01), NANOG, NCF2, ELF and TGF-β at a cut of > 0.314, > 0.392, 0.349 and 0.333 respectively showed sensitivity (96.5%, 98.8%, 95.3%, 98.8%) and specificity of (95.3%, 92.6%, 89.5%, 93.8%) respectively in diagnosing colonic adenocarcinoma. Sirt-1 protein level was significantly highly expressed in colorectal adenocarcinoma compared to normal and adenoma colonic tissue and positively correlated with NANOG.

CONCLUSION: Over expression of NANOG, p38α , NCF2, ELF and TGF-β genes in both cases of adenocarcinoma and adenoma could have a diagnostic value. SIRT-1 and NANOG are high correlated biological markers for diagnosis and prognosis follow up in patients with adenocarcinoma.

BACKGROUND/AIM: Egypt has the highest prevalence rate of Hepatitis C virus (HCV) infection around the globe, where, chronic hepatits C (CHC) is considered a major health problem. The standard treatment of CHC is combination therapy of pegylated interferon and ribavirin. Successful treatment and sustained virological response (SVR) are only achieved in 30% of patients. Major adverse effects and high cost of the treatment makes predicting the treatment output is an important approach. The aim of this study to find an association between Vitamin D concentration and vitamin D receptor (VDR) polymorphisms with achieving SVR.

METHODS: This is a case control study in which; 250 patients recruited and were divided into 3 groups (100 CHC patients who achieved SVR, 100 CHC patients who did not achieve SVR, and 50 apparently healthy individuals as control). Blood samples were collected to measure vitamin D concentration and 4 VDR polymorphisms (FokI, ApaI, TaqI, and BsmI) were detected using RFLP-PCR.

RESULTS: Non responders were found to have significantly low vitamin D concentration compared to responders and control groups. Concerning VDR polymorphisms, both FokI and TaqI polymorphisms were associated to successful treatment.

CONCLUSION: Vitamin D concentration, FokI, and TaqI may be considered as one of the predictors for the response of CHC patients to combination of pegylated interferon and ribvirin therapy. This article is protected by copyright. All rights reserved.

BACKGROUND AND OBJECTIVE: Human umbilical cord blood (UCB) cells and bone marrow mesenchymal stem cells (BM-MSCs) have numerous advantages as grafts for cell transplantation. We hypothesized differing impacts of human UCB cells and rat BM-MSCs on reversal of hepatic injury and revival of liver function in carbon tetrachloride (CCl4)-induced liver fibrosis.

METHODS: Forty rats were divided into 4 groups; control group, CCl4 group, CCl4/CD34(+) group and CCl4/BM-MSCs group. Blood samples were driven from rats at 4, 8 and 12 weeks to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of collagen Iα, TGF-β, α-SMA, albumin, MMP-2, MMP-9 and TNF-α were assessed by polymerase chain reaction. Histopathological examination of the liver tissue was performed. GFP labeled cells were detected in groups injected with stem cells.

RESULTS: Regarding liver function, CD34(+) were more efficient than BM-MSCs in elevating albumin (P<0.05) and reducing ALT (P<0.05) concentrations. Concerning gene expression, CD34(+) were more effective than BM-MSCs in reducing gene expressions of collagen Iα (P<0.01), TGF-β1 (P<0.01) and α-SMA (P<0.01). Both CD34(+) and BM-MSCs have the same efficacy in reducing TNF-α (P<0.001 and P<0.01, respectively). Furthermore, CD34(+) were more valuable than BM-MSCs in increasing gene expression of albumin (P<0.05) and MMP-9 (P<0.01).

CONCLUSION: Taken together; human UCB CD34(+) stem cells were more efficient in improvement of experimental liver injury than BM-MSCs. This study highlighted an important role of human UCB CD34(+) stem cells in liver fibrosis therapy.

BACKGROUND: Bio-products from stem/progenitor cells, such as extracellular vesicles, are likely a new promising approach for reprogramming resident cells in both acute and chronic kidney disease. Forty CKD patients stage III and IV (eGFR 15-60 mg/ml) have been divided into two groups; twenty patients as treatment group "A" and twenty patients as a matching placebo group "B". Two doses of MSC-derived extracellular vesicles had been administered to patients of group "A". Blood urea, serum creatinine, urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used to assess kidney functions and TNF-α, TGF-β1 and IL-10 have been used to assess the amelioration of the inflammatory immune activity.

RESULTS: Participants in group A exhibited significant improvement of eGFR, serum creatinine level, blood urea and UACR. Patients of the treatment group "A" also exhibited significant increase in plasma levels of TGF-β1, and IL-10 and significant decrease in plasma levels of TNF-α. Participants of the control group B did not show significant improvement in any of the previously mentioned parameters at any time point of the study period.

CONCLUSION: Administration of cell-free cord-blood mesenchymal stem cells derived extracellular vesicles (CF-CB-MSCs-EVs) is safe and can ameliorate the inflammatory immune reaction and improve the overall kidney function in grade III-IV CKD patients.

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

Abbreviations
CTO, chronic total occlusion; CAG, coronary angiography; AMI, acute myocardial infarction; DILDL-FITC labeled UEA-11, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine-labeled acetylated LDL (DiLDL,) and FITC-labeled Ulex europaeus agglutinin-1; MVD, multivessel disease; CFU, colony forming unit