In Vitro and In Vivo Comparative Analysis of Differentially Expressed Genes and Signaling Pathways in Breast Cancer Cells on Interaction with Mesenchymal Stem Cells.

The interaction of breast cancer cells (BCC) with mesenchymal stem cells (MSC) plays a vital role in influencing the gene expression in breast cancer cells and thereby its uncontrolled proliferation, metastasis, and drug resistance. The extent of MSC governing the BCC or the extent of BCC influencing the MSC is a complex process, and the interaction strongly depends upon conditions such as the presence or absence of other cell types and in vivo tumor microenvironment or simple in vitro conditions. Hence, understanding this interaction through gene expression profiling may provide key insights about potential genes which can be targeted for breast cancer treatment. In the current study, in vitro microarray dataset and in vivo RNA-seq dataset of BCC on interaction with the MSC were downloaded from NCBI GEO database and analyzed for differentially expressed genes (DEGs), gene ontology (GO) term enrichment, and Reactome pathway analysis. To target the genes which have similar effect on both in vitro and in vivo, a comparative analysis was performed, 24 genes were commonly upregulated in both in vitro and in vivo datasets, while no common downregulated genes were observed. Out of which, 16 significant genes based upon fold change (logFC > 2) are identified for manipulating the interactions between MSC and BCC. Among them, 6 of the identified genes (FSTL1, LOX, SERPINE1, INHBA, FN1, and VEGFA) have already been reported to be upregulated in BCC on interaction with MSC by various studies. Further experiments need to be conducted to understand the role of remaining 10 identified genes (EFEMP1, IGFBP3, EDIL3, IFITM1, IGFBP4, ITGA5, SLC3A2, HRH1, PPP1R15A, and NNMT) in MSC-BCC interaction. In addition to the reported significant genes and its associated pathways, the expression of long non-coding RNA identified in this study may increase our understanding about the way MSC interacts with BCC and accelerate MSC-based treatment strategies for breast cancer.

Advances in 3D printing of composite scaffolds for the repairment of bone tissue associated defects.

The conventional methods of using autografts and allografts for repairing defects in bone, the osteochondral bone, and the cartilage tissue have many disadvantages, like donor site morbidity and shortage of donors. Moreover, only 30% of the implanted grafts are shown to be successful in treating the defects. Hence, exploring alternative techniques such as tissue engineering to treat bone tissue associated defects is promising as it eliminates the above-mentioned limitations. To enhance the mechanical and biological properties of the tissue engineered product, it is essential to fabricate the scaffold used in tissue engineering by the combination of various biomaterials. Three-dimensional (3D) printing, with its ability to print composite materials and with complex geometry seems to have a huge potential in scaffold fabrication technique for engineering bone associated tissues. This review summarizes the recent applications and future perspectives of 3D printing technologies in the fabrication of composite scaffolds used in bone, osteochondral, and cartilage tissue engineering. Key developments in the field of 3D printing technologies involves the incorporation of various biomaterials and cells in printing composite scaffolds mimicking physiologically relevant complex geometry and gradient porosity. Much recently, the emerging trend of printing smart scaffolds which can respond to external stimulus such as temperature, pH and magnetic field, known as 4D printing is gaining immense popularity and can be considered as the future of 3D printing applications in the field of tissue engineering.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells.

Mesenchymal stem cells, because of their high proliferation, differentiation, regenerative capacity, and ease of availability, have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and act against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra- cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that act as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as they are the leading members of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.