The process of bone repair has always been a natural mystery. Although bones do repair themselves, supplemental treatment is required for the initiation of the self-regeneration process. Predominantly, surgical procedures are employed for bone regeneration. Recently, cell-based therapy for bone regeneration has proven to be more effective than traditional methods, as it eliminates the immune risk and painful surgeries. In clinical trials, various stem cells, especially mesenchymal stem cells, have shown to be more efficient for the treatment of several bone-related diseases, such as non-union fracture, osteogenesis imperfecta, osteosarcoma, and osteoporosis. Furthermore, the stem cells grown in a suitable three-dimensional scaffold support were found to be more efficient for osteogenesis. It has been shown that the three-dimensional bioscaffolds support and simulate an in vivo environment, which helps in differentiation of stem cells into bone cells. Bone regeneration in patients with bone disorders can be improved through modification of stem cells with several osteogenic factors or using stem cells as carriers for osteogenic factors. In this review, we focused on the various types of stem cells and scaffolds that are being used for bone regeneration. In addition, the molecular mechanisms of various transcription factors, signaling pathways that support bone regeneration and the senescence of the stem cells, which limits bone regeneration, have been discussed.

Simazine and propazine are selective triazine herbicides currently in use to control broad-leaved weeds and annual grasses around the world. Bisphenol A (BPA) is an industrial chemical used in the production of polycarbonate plastics often found in consumer goods, such as plastic containers, baby bottles etc. These synthetic compounds are known to increase the risk of cancer, cause adverse reproductive effect in reptiles, mammals, birds, humans, and lead to other health problems. They have become some of the principal agents of contamination in water bodies around the world through herbicide runoff, industrial waste and leaching. Some triazines such as atrazine are banned in most European countries for over ten years due to their adverse reproductive effect in mammals, birds and humans; however propazine and simazine are still in use around the world. The removal of these compounds from contaminated water is an exigent challenge. In this study, we investigated their affinity for the surface of nanoparticles (NPS) and standard metallic oxides in an effort to exploit the unique potential applications of NPS for water purification systems. We studied the adsorption of the two triazines and BPA on the surface of NPS of iron (III) oxide, NPS of carbon, bulk iron (III) oxide and aluminum oxide at pH 6 and pH 8 using UV-Visible spectroscopy. Result indicates that these compounds have different affinity towards the surface of metallic oxides and carbon at various pHs. In general, there is relatively high adsorption of some of these compounds on the surface of NPS compared to bulk particles. NPS of carbon have shown the highest affinity for all the three compounds. The lower pH was found to be favorable for all of the compounds except for BPA. BPA have shown high adsorption at pH 8 than at pH 6.

Background: Current stem cells therapy for ischemic cardiomyopathy is effective only about 2-4% in improving cardiac function. In search of novel therapy, we have developed a safe mRNA-based reprogramming of non-invasively derived human urinary epithelial cells into induced pluripotent stem cells (iPSC), and subsequently differentiated them into mesenchymal stem cells (iMSC). We examined therapeutic potential of iMSC in comparison with adult umbilical cord mesenchymal stem cells (MSC). Hypothesis: Autologous iMSC and their exosomes possess an enhanced cardioprotective characteristics compared to MSC. Methods and Results: The generated iMSC and their exosomes (ExoQuick reagent) offered an enhanced protection of human iPSC-derived cardiomyocytes (iCMC) from injuries of (i) angiotensin-II (Ang, 10 μM for 24 h) and (ii) 6 hrs of 1% hypoxia and 24 hrs of reoxygenation, in comparison with their MSC controls. The cardiomyocyte protection was studied through measurement of mitochondrial membrane potential (JC1 dye), intracellular reactive oxygen species (CM-H2DCFDA), in situ cell death by apoptosis, and qRT-PCR expression of survival and proinflammatory genes (BCL2, BAD, TNFA and IL6). Treatment with iMSC-derived exosomes alone enhanced the expression of NRF2, a major regulator of cytoprotective genes in protecting Ang-challenged iCMC. The specific role of iMSC exosomal RNAs and proteins in mediating cardioprotection against Ang-induced injury was identified through in situ cell death assay using the exosomes treated with either RNase A (0.5 μg/μl for 20 min at 37 0 C) or proteinase K (0.05 μg/μl for 10 min at 37 0 C) (Fig.1) . Exosomal noncoding RNA analysis by qRT-PCR revealed the presence of inflammation-associated small nucleolar RNAs such as SNORD32A, SNORD33, SNORD34 and SNORD35A. The transfer of exosomal RNAs into the host cardiac cells was augmented in presence of Ang, identified using 0.5 mM ethynyl uridine-labelled exosomes and detected using Click-iT RNA imaging reagents. All experiments were carried out in triplicates. In vivo studies are in progress. Conclusion: In comparison with adult MSC, non-invasively derived autologous iMSC and their exosomes elicit enhanced cardioprotection and may provide an alternative source of cells or cell-free therapy for treating ischemic cardiomyopathy.

Background: Hutchinson-Gilford progeria (HGP) is a rare genetic disorder in which children age rapidly. They suffer from atherosclerosis, cardiovascular diseases, and strokes. The LMNA variant c.1824C>T accounts for ~90% of HGP cases. This variant causes an abnormal Lamin A protein called progerin. The detailed molecular mechanisms of Lamin A in the heart remain elusive due to the lack of appropriate in vitro models. Hypothesis: We hypothesize that HGP patient’s induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMCs) will provide a model platform to study the cardio-pathologic mechanisms associated with progeria. Methods and Results: We performed in silico analysis of LMNA variant c.1824C>T to determine its effects on Lamin A structure and stability. For validation , skin fibroblasts (SFs) from a de-identified HGP patient (hPGP1, proband) and parents were obtained from the Progeria Foundation. Through Sanger sequencing (Fig 1A) and restriction fragment length polymorphism, with enzyme EciI , targeting Lamin A, we characterized hPGP1-SFs as heterozygous mutants for variant c.1824 C>T. Then, we reprogrammed the three SFs into iPSCs (Fig 1B) using a safe mRNA-based reprogramming method , and differentiated them into iCMCs, which gained beating on day 7. We found that hPGP1-iCMCs (Fig 1C) had an irregular contractile function by Particle Image Velocimetry Analysis and decreased cardiac-specific gene and protein expressions by qRT-PCR and Western Blot. Conclusions: We successfully generated iCMCs from a progeria patient carrying LMNA variant c.1824C>T. These iCMCs were found to be functionally and structurally defective when compared to normal iCMCs. Our in vitro model will help elucidate the role of Lamin A and the cardio-pathologic mechanisms associated with progeria.