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Schistosomiasis is a neglected tropical disease. Egg-induced granuloma formation and tissue fibrosis are the main causes of the high morbidity and mortality of schistosomiasis. Mesenchymal stem cells (MSCs)-derived exosomes play an important role with a superior safety profile than MSCs in the treatment of liver fibrosis. Therefore, the aim of this study was to investigate the potential therapeutic effect of MSCs-derived exosomes on schistosomal hepatic fibrosis. Exosomes were isolated from bone marrow MSCs and characterized. A total of 85 mice were divided into four groups: group I (control group), group II (PZQ group) infected and treated with PZQ, group III (EXO group) infected and treated with MSCs-derived exosomes and group IV (PZQ+EXO group) infected and treated with both PZQ and MSCs-derived exosomes. Assessment of treatment efficacy was evaluated by histopathological and immunohistochemical examination of liver sections by proliferating cell nuclear antigen (PCNA) and nuclear factor-κB (NF-κB). The results showed significant reduction of the number and diameter of hepatic granulomas, hepatic fibrosis, upregulation of PCNA expression and reduction of NF-κB expression in EXO and PZQ+EXO groups as compared to other groups at all durations post infection. Additionally, more improvement was observed in PZQ+EXO group. In conclusion, MSCs-derived exosomes are a promising agent for the treatment of schistosomal hepatic fibrosis, and their combination with PZQ shows a synergistic action including antifibrotic and anti-inflammatory effects. However, further studies are required to establish their functional components and their mechanisms of action. [ABSTRACT FROM AUTHOR]

The current study was conducted to determine to what extent human platelet lysate (HPL) can be used to enhance the growth of three cell lines used for propagation of Bovine Ephemeral Fever Virus (BEFV) and Rabies virus (RV) for vaccine production. HPL; Fetal Calf Serum (FCS) and Newborn Calf Serum (NBCS) were used as supplements to the used cell culture medium (Minimum Essential Medium "MEM") for passaging of three cell lines including baby hamster kidney (BHK-21); African green monkey kidney (VERO) and Madin Derby canine kidney (MDCK). Through three successive cell culture passages; for each cell line; it was found that HPL supported growth and propagation of BHK-21, VERO and MDCK cell lines without altering their morphologic and functional characteristics. It has been accepted as a suitable alternative to FBS and NBCS, and it can be used in vaccinal production. [ABSTRACT FROM AUTHOR]

Background: Bone tissue regeneration requires the development of safe and effective biodegradable scaffolds made of biomaterials with bone composition mimic coating. This study aimed to assess the osteoinduction potentiality of pure Mg- implant before and after coating with different CNT composite coating; CNT and chitosan alone or hybridized with calcium phosphate. Methods: UDMSCs were cultured on the Pure Mg, Mg disks coated by CNT and Chitosan, Mg disks coated by CNT/ Chitosan/ di-calcium phosphate, and Mg disks coated by CNT/ Chitosan /HA (fine and coarse). The osteoblasts’ differentiation was assessed by alizarin red staining. Crystal violet was used to assess cell viability percent of each of the investigated surfaces. The functionality of osteoblasts was assessed by ALP and Ca amount. Results: All the investigated surfaces led to an osteoblasts differentiation except the surface hybrid with di-Cap. Least cell viability was recorded with pure Mg and Mg coated by CNT and Chitosan composite 85 and 80%, respectively. Mg coated by CNT / Chitosan/di-Cap composite recorded the least amount of ALP ad Ca amount; 0.8 ± 0.39 And 0.8 ±0.27, respectively. Whereas the composite coating contained CNT/Chitosan and HA coarse hybrid with CNT / Chitosan recorded the highest significant higher ALP and Ca amount. Conclusions: Pure Mg surface coated with CNT, Chitosan, and HA composite has an osteoinductive potentiality. Using Mg surface coated by calcium phosphate compounds hybrid with CNT and Chitosan enhanced the viability and lessened the cytotoxicity of the osteoblasts. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) and hepatocytes are considered valuable candidates for cell-based therapy. The use of free zoonotic media, as purified platelets derived growth factors (L-GF) and human platelet lysate (hPL), instead of using fetal bovine serum (FBS) to support the growth and proliferation of these cells could be used as a promising therapeutic tool in hepatic regeneration. This study aimed to evaluate the usage of purified platelet derived growth factors and platelet lysate in both MSCs and hepatocyte cultures and to compare them with the usage of FBS. MSCs and hepatocytes were cultured in growth media supplemented with L-GF or hPL and compared them to their culture in growth media supplemented with FBS. Cells were subjected to population doubling (PD) and generation time (GT) calculations. The best result for MSCs was that obtained by using 10% hPL or 10% FBS with the highest cell count, highest viability and shortest incubation time needed to reach confluency compared to supplementation with 10%, 20% or 30% L-GF. As for hepatocyte culture, the use of 10% FBS for supplementation of media used for hepatic cell proliferation showed better performance regarding cell count, viability, and incubation time to reach confluency compared to the use of either hPL or L-GF. In conclusion, our study showed that 10% hPL had the best results in MSCs culture which suggests that hPL could be a better alternative for the development of xenofree stem cell culture that can be used for many clinical applications. On the other hand, 10% FBS showed the best results in hepatocyte culture., (Copyright© by the Egyptian Association of Immunologists.)

Background: Liver cancer stem cells (LCSCs) are a subpopulation of tumor cells that can drive cancer initiation and relapses. Because of their significance, researchers are looking for biomarkers that characterize or regulate LCSCs so that they can be used as targets for the diagnosis and treatment of chronic liver diseases and hepatocellular carcinoma (HCC)., Methodology: Six groups of patients having hepatitis C virus (HCV), HCV + cirrhosis, HCV + HCC, hepatitis B virus (HBV), HBV + cirrhosis, or HBV + HCC, in addition to a control group, were subjected to the measurement of LCSCs levels and analysis of miR-1290 and miR-1825 expression., Results: The percentages of the CD133/EpCAM-expressing LCSCs were increased in viral hepatitis and cirrhosis groups, compared to the control group. HCC patients had the highest percentages of LCSCs. CD133/EpCAM-expressing cells showed significant correlations with stemness-associated miRNAs; miR-1290 and miR-1825. Also, the miR-1290 and miR-1825 were significantly up-regulated in viral hepatitis-associated cirrhosis and HCC groups. Moreover, in HCV + HCC, miR-1290 and miR-1825 expression was significantly positively correlated with tumor size and number. However, only miR-1825 could distinguish between HCV- and HBV-associated HCC groups. MiR-1290 exhibited the highest sensitivity and specificity for detecting HCC, followed by miR-1825 and CD133/EpCAM-expressing LCSCs., Conclusions: These findings indicate the relevance of CD133/EpCAM-expressing cells in the pathogenesis of liver cirrhosis and HCC developed as a consequence of either chronic HCV or HBV infection. Accordingly, CD133/EpCAM-expressing cells, miR-1290, and miR-1825, could serve as promising diagnostic and prognostic biomarkers as well as therapeutic targets in patients suffering from liver cirrhosis or HCC., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors.)

Background: Therapeutic microRNAs (miRNAs) delivery holds a lot of promise for treating human malignancies. So, this study was carried out to examine the potential of miR-122 mimic and/or miR-221 inhibitor as an innovative therapeutic strategy for HCC in an animal model., Methodology: Mice were categorized into five groups comprising: (1) a normal control group, (2) an HCC group subjected to diethylnitrosamine (DEN) injection for 12 weeks, (3) a miR-122 mimic-treated HCC group, (4) a miR-221 inhibitor-treated HCC group, and (5) a miR-122 mimic/miR-221 inhibitor-treated HCC group. After 16 weeks, all animals were sacrificed and underwent biochemical, miRNAs and genes expression, histopathological, and immunohistochemical examinations., Results: The miR-122 mimic/miR-221 inhibitor combination dramatically reduced the levels of pro-inflammatory, liver cancer, angiogenesis, and cell proliferation markers when compared to either treatment alone. It also down-regulated the expression of cyclin D1, TGF-β, and β-catenin genes, which are involved in promoting cell cycle progression and cancer cell proliferation. Furthermore, it caused the resolution of nearly all the histological malignant features as well as the reduction of malignant cellular markers, including α-smooth muscle actin, arginase-1, and tropomyosin-1., Conclusions: The co-treatment with miR-122 mimic and miR-221 inhibitor amplifies the benefits of either treatment on HCC through targeting the SENP1 and ARF4 genes, respectively. This combination can inhibit cancer cell proliferation and angiogenesis while inducing tumor apoptosis and necrosis. This study demonstrates the therapeutic potential of reversing a dysregulated miRNAs expression pattern in HCC. As a result, future research should concentrate on turning miRNA understanding into therapeutic applications., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Authors.)