Clonal selection parallels between normal and cancer tissues.

Clonal selection and drift drive both normal tissue and cancer development. However, the biological mechanisms and environmental conditions underpinning these processes remain to be elucidated. Clonal selection models are centered in Darwinian evolutionary theory, where some clones with the fittest features are selected and populate the tissue or tumor. We suggest that different subclasses of stem cells, each of which is responsible for a distinct feature of the selection process, share common features between normal and cancer conditions. While active stem cells populate the tissue, dormant cells account for tissue replenishment/regeneration in both normal and cancerous tissues. We also discuss potential mechanisms that drive clonal drift, their interactions with clonal selection, and their similarities during normal and cancer tissue development.

Polyvinyl alcohol modified polyvinylidene fluoride-graphene oxide scaffold promotes osteogenic differentiation potential of human induced pluripotent stem cells.

Tissue engineering is fast becoming a key approach in bone medicine studies. Designing the ideally desirable combination of stem cells and scaffolds are at the hurt of efforts for producing implantable bone substitutes. Clinical application of stem cells could be associated with serious limitations, and engineering scaffolds that are able to imitate the important features of extracellular matrix is a major area of challenges within the field. In this study, electrospun scaffolds of polyvinylidene fluoride (PVDF), PVDF-graphene oxide (GO), PVDF-polyvinyl alcohol (PVA) and PVDF-PVA-GO were fabricated to study the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs) while cultured on fabricated scaffolds. Scanning electron microscopy study, viability assay, relative gene expression analysis, immunocytochemistry, alkaline phosphates activity, and calcium content assays confirmed that the osteogenesis rate of hiPSCs cultured on PVDF-PVA-Go is significantly higher than other scaffolds. Here, we showed that the biocompatible, nontoxic, flexible, piezoelectric, highly porous and interconnected three-dimensional structure of electrospun PVDF-PVA-Go scaffold in combination with hiPSCs (as the stem cells with significant advantageous in comparison to other types) makes them a highly promising scaffold-stem cell system for bone remodeling medicine. There was no evidence for the superiority of PVDF-GO or PVDF-PVA scaffold for osteogenesis, compared to each other; however both of them showed better potentials as to PVDF scaffold.

In vitro osteogenic differentiation potential of the human induced pluripotent stem cells augments when grown on Graphene oxide-modified nanofibers.

Due to the several limitations that surgeons are faced during bone tissue implantation there are daily increases in introducing new cell-co-polymer composites for use in bone tissue engineering approaches. In this study tried to develop a suitable nanostructured bio-composite for enhancing osteogenic differentiation of the human induced pluripotent stem cells (iPSCs). Polyvinylidene fluoride-Graphene oxide (PVDF-GO) nanofibers was fabricated by electrospinning and then characterized using scanning electron microscope, tensile and viability assays. After that osteogenic differentiation of the iPSCs was investigated in three groups, including PVDF, PVDF-GO and tissue culture plate as a control group. Alkaline phosphatase activity and calcium content of the iPSCs cultured on PVDF-GO were significantly higher than those cultured on other groups. In addition, Runx2, osteocalcin and osteonectin genes were up regulated in iPSCs cultured on PVDF-GO significantly higher than those cells cultured on PVDF and control. Finally, osteocalcin and osteopontin proteins expression evaluated and the results confirmed higher osteoinductivity of the PVDF-GO nanofibers in comparison with the PVDF nanofibers. According to the results, it was demonstrated that PVDF-GO nanofibers have a great osteoinductive potential and taking together iPSCs-PVDF-GO nanofibrous construct can be an appropriate bio-implant to use for bone tissue engineering applications.

CD73; a key ectonucleotidase in the development of breast cancer: Recent advances and perspectives.

Tumor cell invasion and metastasis are the definitive cause of mortality in breast cancer (BC). Hypoxia and pro-inflammatory cytokines upregulate the CD73 gene in the tumor microenvironment. Subsequently, CD73 triggers molecular and cellular signaling pathways by both enzymatic and nonenzymatic pathways, which finally leads to breast tumor progression and development. In this paper, we summarize current advances in the understanding of CD73-driven mechanisms that promote BC development and mortality. Furthermore, we evaluate the therapeutic potential of CD73 targeting in BC.

A comprehensive overview on utilizing electromagnetic fields in bone regenerative medicine.

Stem cells are one of the most important sources to develope  a new strategy for repairing bone lesions through tissue engineering. Osteogenic differentiation of stem cells can be affected by various factors such as biological, chemical, physiological, and physical ones. The application of ELF-EMFs has been the subject of many research in bone tissue engineering and evidence suggests that this exogenous physical stimulus can promote osteogenic differentiation in several types of  cells. The purpose of this paper is to review the current knowledge on the effects of EMFs on stem cells in bone tissue engineering studies. We recapitulated and analyzed 39 articles that were focused on the application of EMFs for bone tissue engineering purposes. We tabulated scattered information from these articles for easy use and tried to provide an overview of conducted research and identify the knowledge gaps in the field.

Osteogenic differentiation potential of mesenchymal stem cells cultured on nanofibrous scaffold improved in the presence of pulsed electromagnetic field.

Nowadays, tissue engineering by using stem cells in combination with scaffolds and bioactive molecules has made significant contributions to the regeneration of damaged bone tissues. Since the usage of bioactive molecules including, growth factors to induce differentiation is safety limited in clinical applications, and it has also been previously observed that extremely low frequency pulsed electromagnetic fields (PEMF) can be effective in the enhancement of proliferation rate and osteogenic differentiation of stem cells, the aim of this study was investigating the osteoinductive potential of PEMF in combination with Poly(caprolactone) (PCL) nanofibrous scaffold. To achieve this aim, Adipose-derived mesenchymal stem cells (ADSCs) isolated and characterized and then osteogenic differentiation of them was investigated after culturing on the surface of PCL scaffold under treatments of PEMF, PEMF plus osteogenic medium (OM) and OM. Analysis of common osteogenic markers such as Alizarin red staining, ALP activity, calcium content and four important bone-related genes in days of 7, 14, and 21 confirmed that the effects of PEMF on the osteogenic differentiation of ADSCs are very similar to the effects of osteogenic medium. Thus, regarding the immunological concerns about the application of bioactive molecules for tissue engineering, PEMF could be a good alternative for osteogenic medium. Although, results were showed a synergetic effect for simultaneous application of PEMF and PCL scaffold in the osteogenesis process of ADSCs. Taking together, ADSCs-seeded PCL nanofibrous scaffold in combination with PEMF could be a great option for use in bone tissue engineering applications.

Human RNAi pathway: crosstalk with organelles and cells.

Understanding gene regulation mechanisms has been a serious challenge in biology. As a novel mechanism, small non-coding RNAs are an alternative means of gene regulation in a specific and efficient manner. There are growing reports on regulatory roles of these RNAs including transcriptional gene silencing/activation and post-transcriptional gene silencing events. Also, there are several known small non-coding RNAs which all work through RNA interference pathway. Interestingly, these small RNAs are secreted from cells toward targeted cells presenting new communication approach in cell-cell or cell-organ signal transduction. In fact, understanding cellular and molecular basis of these pathways will strongly improve developing targeted therapies and potent and specific regulatory tools. This study will review some of the most recent findings in this subject and will introduce a super-pathway RNA interference-based small RNA silencing network.