Cell and Tissue Journal

Abstract Nanotechnology is an emerging branch of science that is widely used in various fields including medicine. Nanoparticles (NPs) are produced by various compounds in size, shape, and different chemical properties, which can be used in a variety of biological and biomedical applications. Metal NPs are used widely in many fields and have various properties making them appropriate for use in medical applications.
Zinc is an essential trace element for almost all living organisms. Due to possessing a significant role in versatile biological processes, including fetal development, natural growth, wound healing, metabolism, immunity, cognitive functions, sperm generation, bone mineralization, neurological, and enzymatic processes.
In recent decades, zinc oxide NPs have been one of the most popular types of NPs with numerous biological applications due to their biocompatibility and low toxicity and are used in a wide range of commercial applications including applications in many different industries such as pharmaceuticals, textiles, dyes, rubber, tissue engineering, antibacterial agents, and anti-cancer. Nowadays, significant scientific interest has been directed toward the application of nanomaterials in the modulation of stem cell proliferation and differentiation for further application in regenerative medicine. Zinc is one of the most plentiful trace metals in the human body and was reported to be essential for the regeneration of bone. ZnO-NPs exhibit attractive antibacterial properties. Particular emphasis was given to bactericidal and bacteriostatic mechanisms with a focus on the generation of reactive oxygen species (ROS). ROS has been a major factor for several mechanisms including cell wall damage due to ZnO-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force, and uptake of toxic dissolved zinc ions.  ZnO NPs present certain cytotoxicity in cancer cells and induce cancer cell death via the apoptosis signaling pathway. This autophagy induction was positively correlated with the dissolution of ZnO NPs in lysosomes to release zinc ions, and zinc ions released from ZnO NPs were able to damage lysosomes, leading to impaired autophagic flux and mitochondria.
ZnO nanostructures, featuring antimicrobial activity, osteogenesis, and angiogenesis, have been also combined with additive manufacturing technologies with the final aim of designing novel advanced hybrid scaffolds for tissue engineering.
Zinc deficiency is positively correlated with diabetes and may also affect the progress of Type 2 diabetes. Several zinc complexes have been synthesized and proven to be effective in rodent models of diabetes.
ROS are generated by metal oxide nanoparticles which considerably help in fibroblast proliferation. The interlinkage of the fibroblast cells and zinc oxide nanoparticles was impacted by the surface area and particle size of the nanoparticles. Zinc oxide nanoparticles dressing increases apoptosis, bacteria clearance, platelet activation, tissue necrosis, re-epithelialization, tissue scar formation, debris removal, angiogenesis, and stem cell activation through wound healing. Nanoparticle-based drug delivery systems (DDS) can overcome the aforementioned limitations by releasing the drugs in a slow and sustained manner and delivering them to the desired area of the body system. This article provides an overview of some of the research relating to the use of zinc oxide nanoparticles in biological sciences.

Abstract Aim: Cell therapy using mesenchymal stem cells (MSCs) can be a promising tool in regenerative medicine. One of the richest sources of mesenchymal stem cells is fetal bone marrow. Silymarin has strong antioxidant and anti-inflammatory activities with a positive effect on the proliferation of some cells as well as anti-osteoporosis properties. This study aimed to show the effect of silymarin on the differentiation of mesenchymal stem cells derived from the bone marrow of sheep embryos into the osteogenic line.
Materials and Methods: Mesenchymal stem cells were isolated from the bone marrow of sheep embryos. MTT test was performed to investigate the cytotoxicity of silymarin on cells at different concentrations for 24 and 72 hours. Then, cells in one of 8 groups 1: negative control; 2: treated with 10 μmol/liter silymarin in the usual environment, 3: treated with 20 μmol/liter silymarin in the usual environment, 4: treated with 100 μmol/liter estradiol in the usual environment, 5: positive control, 6: treatment treated with 10 μmol/liter silymarin in the differentiation medium, 7: treated with 20 μmol/liter silymarin in the differentiation medium, 8: treated with 100 μmol/liter in the differentiation medium, were cultured for 21 days. To determine the osteogenic differentiation of cells, the deposition of hydroxyapatite ions was examined using alizarin staining, and also, the amount of ALP enzyme secretion was also measured in the studied groups. Results: Comparing the average optical absorption of cells at different concentrations between 24 and 72 hours after treatment showed that the average optical absorption of cells at zero concentration of silymarin after 72 hours of treatment decreased in comparison with those treated for 24 hours (P<0.05), but no significant difference was observed in other concentrations (P>0.05). Examining the level of ALP enzyme secretion, 21 days after treatment with silymarin in the studied groups showed that the highest level of enzyme secretion was in group 8 (P≤0.05). The lowest amount of enzyme secretion was observed in group 1 (negative control) and then in group 2 and group 3 respectively (P<0.05). No significant difference was observed between groups 4, 5, and 6 (P>0.05). Based on the alizarin red staining results, calcium ions deposition was observed in all the groups related to the differentiation medium, which increased in groups 8, 7, 6, and 5, respectively. In the groups cultured in the usual environment, there was no calcification in group 1 and the amount of calcification increased in groups 2, 3, and 4, respectively. In total, the amount of calcification in the differentiation environment groups was higher in comparison with the usual environment.
Conclusion: During this study, Silymarin had no toxic effect on the mesenchymal stem cells derived from the bone marrow of sheep embryos in the studied concentrations after 24 and 72 hours of treatment. It increased the differentiation of the cells into the osteogenic lineage in a concentration-dependent manner. Therefore, it seems that with further studies and identification of the molecular pathways of silymarin's effect, it can be used in cell therapy in order to repair bone lesions.

Abstract Aim: The aim of this study was to compare the anti-proliferative and apoptotic effects of hydroalcoholic extracts of different herbal medicines (Achillea wilhelmsii, Silybum marianumseed, Echinacea purpurea, Adiantum capillus-venerisand apricot kernel) against breast cancer cells (Mcf-7).
Material and method: For this purpose, the plants were dried and milled, then, soaked in 70% ethanol for 72 hours and their extracts were extracted using a rotary evaporator.Different concentrations of herbal extracts (12.5, 25, 50 and 100 μg/ml) were added to the cancer cell culture medium and their cytotoxicity and apoptotic effects were investigated after 24h by MTT assay and acridine orange - ethidium bromide staining, respectively.Data was analyzed by SPSS software at the significant level of 5%.
Results: Addition of the highestconcentration of all extracts to the culture mediumshowed the most significant anti-proliferative and apoptotic effects (p < 0.05) compared to other concentrations of the same extracts.Also, among the high concentrations (100μg/ml), the highest cell cytotoxicity effects were related to the extracts of Echinacea purpureaand Adiantum capillus-veneris (p < 0.05).
Conclusion: The results of this study indicated that the addition of Echinacea purpurea and Adiantum capillus-venerisextractsto the cell culturesin high concentrationshad the most significant anti proliferative and apoptotic effects on breast cancer cells in comparison with other plant extractsand concentrations.
 

Abstract Aim: The aim of the present study was to evaluate the effects of different concentrations of Chir99021 on ovine fetal marrow-derived mesenchymal stem cells (BM-MSCs) expansion in culture.  Material and Methods: BM-MSCs were isolated from ovine fetal and cultured. Passaged-3 cells were examined for their differentiation potential into osteocytes and adipocytes. In the present study, BM-MSCs from ovine fetal were plated in the presence of 0, 0.5, 1, 1.5, 3 and 5 μM of Chir9902. During the cultivation period, the cultures were statistically compared in terms of induces of cell growth including the number of colonies, population doubling number (PDN), doubling time (DT) and the number of viable cells. Furthermore, expression of the beta-catenin was evaluated. The culture without Chir99021 was taken as the control group.  Results: Our findings indicated that, addition of 0.5 and 1 µM of Chir99021 to medium significantly improved overall proliferation compared to that of control group as well as 5µM of Chir99021(p < 0.05). Furthermore, Five days after treatment with small molecule showed that the treatments with 0.5 and 1 µM Chir99021 formed higher Colony Forming Unit-Fibroblast (CFU-F) compared to control and 5 µM of Chir99021. The expression of beta-catenin was significantly higher in culture supplemented with 1 μM of Chir99021 compared to that in groups containing 0.5 and 1.5 μM (p < 0.05). Conclusion: In conclusion, using Chir99021 at concentration of 1 μM could enhance in vitro proliferation of ovine fetal BM-MSC; however administration of high concentration of this small molecule had toxic effects on these cells proliferation.