Current Therapeutic Strategies for Stem Cell-Based Cartilage Regeneration

The process of cartilage destruction in the diarthrodial joint is progressive and irreversible. This destruction is extremely difficult to manage and frustrates researchers, clinicians, and patients. Patients often take medication to control their pain. Surgery is usually performed when pain becomes uncontrollable or joint function completely fails. There is an unmet clinical need for a regenerative strategy to treat cartilage defect without surgery due to the lack of a suitable regenerative strategy. Clinicians and scientists have tried to address this using stem cells, which have a regenerative potential in various tissues. Cartilage may be an ideal target for stem cell treatment because it has a notoriously poor regenerative potential. In this review, we describe past, present, and future strategies to regenerate cartilage in patients. Specifically, this review compares a surgical regenerative technique (microfracture) and cell therapy, cell therapy with and without a scaffold, and therapy with nonaggregated and aggregated cells. We also review the chondrogenic potential of cells according to their origin, including autologous chondrocytes, mesenchymal stem cells, and induced pluripotent stem cells

Fabrication of Modified MMT/Glass/Vinylester Multiscale Composites and Their Mechanical Properties

Montmorillonite (MMT) may become a preferred filler material for fiber-reinforced polymer (FRP) composites due to its high aspect ratio, large surface area, and low charge density. In the present paper, MMT/glass/vinylester multiscale composites are prepared with untreated and surface-treated MMT clay particles with an MMT content of 1.0 wt%. Effects of surface treatment on mechanical properties of MMT/glass/vinylester multiscale composites are investigated through tensile and bending tests, which revealed enhanced mechanical properties in the case of surface-treated MMT. Thermal properties are studied through thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA). X-Ray diffraction is performed to investigate the interaction between MMT and the matrix. Fourier Transform Infrared (FTIR) is also performed for both untreated and surface-treated MMT. Furthermore, Field Emission-Scanning Electron Microscope (FE-SEM) is conducted to investigate the path of fracture propagation within the composite surface, showing that the surface-treated MMT based multiscale composite has better interactions with the host matrix than the untreated MMT multiscale composites. These composites with enhanced mechanical strength can be used for various mechanical applications

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

Background Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts expressed TLR2 and produced IL-6 in response to TLR2 stimulation. Conclusion Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under sterile injury by creating a negative-feedback loop to suppress the upstream TLR2–IL-6 axis that drives corneal nerve loss

Enhanced Coupling Between Soft Ferromagnetism and Displacive Ferroelectricity in the Pb‐Site Modified PbFe1/2_{1/2}Nb1/2_{1/2}O3_{3}

Albeit having great potential toward unprecedented type of applications such as magnetoelectric (ME) sensors and memories, practically useful single-phase multiferroics that show large coupling between ferromagnetism and ferroelectricity at ambient temperatures are still lacking. Here, the discovery of a new type of perovskite ferroelectrics (Pb,M)(Fe$_{1/2}$Nb$_{1/2}$)O$_3$ (M = Fe, Co, Ni) is reported with a magnetically-active metal ion introduced into a cuboctahedrally-coordinated Pb position, which exhibits enhanced ME coupling owing to the development of simultaneous soft-ferromagnetism and lone-pair ferroelectricity persistent above room temperature. These Pb-site engineered (Pb,M)(Fe$_{1/2}$Nb$_{1/2}$)O$_3$ perovskites exhibit a ME coupling coefficient of ≈40–60 ps m$^{−1}$ , a saturated electric polarization of 14–17 μC cm$^{−2}$ and a saturation magnetization of 0.15–0.3 μB f.u$^{−1}$. X-ray absorption spectroscopy combined with first-principles calculations demonstrates that the induced ferromagnetism originates from the ferromagnetic superexchange interaction coming from ≈90° bonding between the magnetic ions at the Pb site. The present discovery of the enhanced ME coupling in the Pb-site engineered perovskite ferroelectrics may provide unforeseen opportunities for applying conventional displacive ferroelectricity in the field of spintronics where ferromagnetism is essentially required

Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCL15), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions play a crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCL15 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis

AKAP12 Mediates Barrier Functions of Fibrotic Scars during CNS Repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process

Obstructive Fibrinous Tracheal Pseudomembrane After Tracheal Intubation: A Case Report

Obstructive fibrinous tracheal pseudomembrane is a rare, but potentially fatal complication associated with endotracheal intubation. It has been known that the formation of tracheal pseudomembrane is related with intracuff pressure during endotracheal intubation or infectious cause. But in the patient described in this case, pseudomembrane formation in the trachea was associated with subglottic epithelial trauma or caustic injuries to the trachea caused by aspirated gastric contents during intubation rather than tracheal ischemia due to high cuff pressure. We report a patient with obstructive fibrinous tracheal pseudomembrane after endotracheal intubation who presented with dyspnea and stridor and was treated successfully with mechanical removal using rigid bronchoscopy

Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair

Because of poor engraftment and safety concerns regarding mesenchymal stem cell (MSC) therapy, MSC-derived exosomes have emerged as an alternative cell-free therapy for myocardial infarction (MI). However, the diffusion of exosomes out of the infarcted heart following injection and the low productivity limit the potential of clinical applications. Here, we developed exosome-mimetic extracellular nanovesicles (NVs) derived from iron oxide nanoparticles (IONPs)-incorporated MSCs (IONP-MSCs). The retention of injected IONP-MSC-derived NVs (IONP-NVs) within the infarcted heart was markedly augmented by magnetic guidance. Furthermore, IONPs significantly increased the levels of therapeutic molecules in IONP-MSCs and IONP-NVs, which can reduce the concern of low exosome productivity. The injection of IONP-NVs into the infarcted heart and magnetic guidance induced an early shift from the inflammation phase to the reparative phase, reduced apoptosis and fibrosis, and enhanced angiogenesis and cardiac function recovery. This approach can enhance the therapeutic potency of an MSC-derived NV therapy.

Three Cases of Non-Surgical Treatment of Stent Loss During Percutaneous Coronary Intervention

Percutaneous coronary intervention with stenting is widely used for ischemic heart disease. Because stent loss, which occurs rarely during the procedure, might have dire consequences, such as bleeding, stent embolism, acute myocardial infarction, emergency coronary artery bypass graft, and death, appropriate treatment is needed as soon as stent loss occurs. We report three cases of stent loss which were successfully treated with three different non-surgical methods