Microengineered Platforms for Co-Cultured Mesenchymal Stem Cells towards Vascularized Bone Tissue Engineering

Bone defects are common disease requiring thorough treatments since the bone is a complex vascularized tissue that is composed of multiple cell types embedded within an intricate extracellular matrix (ECM). For past decades, tissue engineering using cells, proteins, and scaffolds has been suggested as one of the promising approaches for effective bone regeneration. Recently, many researchers have been interested in designing effective platform for tissue regeneration by orchestrating factors involved in microenvironment around tissues. Among factors affecting bone formation, vascularization during bone development and after minor insults via endochondral and intramembranous ossification is especially critical for the long-term support for functional bone. In order to create vascularized bone constructs, the interactions between human mesenchymal stem cells (MSCs) and endothelial cells (ECs) have been investigated using both direct and indirect co-culture studies. Recently, various culture methods including micropatterning techniques, three dimensional scaffolds, and microfluidics have been developed to create micro-engineered platforms that mimic the nature of vascularized bone formation, leading to the creation of functional bone structures. This review focuses on MSCs co-cultured with endothelial cells and micro-engineered platforms to determine the underlying interplay between co-cultured MSCs and vascularized bone constructs, which is ultimately necessary for adequate regeneration of bone defects.

High Correlation between Alu Elements and the Conversion of 3' UTR of mRNAs Processed Pseudogenes

Even though it represents 6 13% of human genomic DNA, Alu sequences are rarely found in coding regions. When in exon region, over 80 % of them are found in 3' untranslated region (UTR). Pseudogenes are an important component of human genome. Their functions are not clearly known and the mechanism of how they are generated is still debatable. Both the Alu and Pseudogenes are important research problems in molecular biology. mRNA is thought to be a prime source of pseudogene and active research is going on its molecular mechanism. We report, for the first time, that mRNAs containing Alu repeats at 3' UTR has a significantly high correlation with processed pseudogenes, suggesting a possibility that Alu containing mRNAs have a high tendency to become processed pseudogenes. It is known that about 10% of all human genes have been transposed. Transposed genes at 3' UTR without Alu repeat have about two processed pseudogenes per gene on average while we found with statistical significance that a transposed gene with Alu had over three processed Pseudogenes on average. Therefore, we propose Alu repeats as a new and important factor in the generation of pseudogenes.