Intra-articular injection is indicated for mild or moderate osteoarthritis (OA). However, the superiority of cell-based injection and the role of diverse cell sources are still unclear. This study ...aimed to compare the therapeutic effect of intra-articular injection with mesenchymal stem cells (MSCs) and cell-free methods for OA treatment.
A literature search of published scientific data was carried out from PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI). Randomized controlled trials (RCTs) compared the efficacy and safety of MSC and cell-free intra-articular injection treatments for OA with at least 6-month follow-up.
Dual network meta-analysis validated the therapeutic advantages of MSC treatments (VAS, Bayesian: 90% versus 10% and SUCRA: 94.9% versus 5.1%; WOMAC total, Bayesian: 83% versus 17% and SUCRA: 90.1% versus 9.9%) but also suggested a potential negative safety induced by cell injection (adverse events, Bayesian: 100% versus 0% and SUCRA: 98.2% versus 1.8%). For the MSC source aspect, adipose mesenchymal stem cells (ADMSCs) and umbilical cord mesenchymal stem cells (UBMSCs) showed a better curative effect on pain relief and function improvement compared with bone marrow mesenchymal stem cells (BMMSCs).
Intra-articular injection of MSCs is associated with more effective pain alleviation and function improvement than cell-free OA treatment. However, the potential complications induced by MSCs should be emphasized. A comparative analysis of the MSC sources showed that ADMSCs and UBMSCs exerted a better anti-arthritic efficacy than BMMSCs. Schematic illustration of MSC-based intra-articular injection for treating OA. Three major MSCs (UBMSCs, ADMSCs, and BMMSCs) are extracted and expanded in vitro. Subsequently, the amplified MSCs are concentrated and injected into the knee joint to treat OA.
The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic ...microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.
Macrophages and bone inflammation Gu, Qiaoli; Yang, Huilin; Shi, Qin
Journal of orthopaedic translation,
07/2017, Letnik:
10, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Bone metabolism is tightly regulated by the immune system. Accelerated bone destruction is observed in many bone diseases, such as rheumatoid arthritis, fracture, and particle-induced osteolysis. ...These pathological conditions are associated with inflammatory responses, suggesting the contribution of inflammation to bone destruction. Macrophages are heterogeneous immune cells and are polarized into the proinflammatory M1 and antiinflammatory M2 phenotypes in different microenvironments. The cytokines produced by macrophages depend on the macrophage activation and polarization. Macrophages and macrophage-derived cytokines are important to bone loss in inflammatory bone disease. Recent studies have shown that macrophages can be detected in bone tissue and interact with bone cells. The interplay between macrophages and bone cells is critical to bone formation and repair. In this article, we focus on the role of macrophages in inflammatory bone diseases, as well as discuss the latest studies about macrophages and bone formation, which will provide new insights into the therapeutic strategy for bone disease.
Abstract
The prodrug approach has emerged as a promising solution to combat bacterial resistance and enhance treatment efficacy against bacterial infections. Here, we report an adenosine triphosphate ...(ATP)-activated prodrug system for on-demand treatment of bacterial infection. The prodrug system benefits from the synergistic action of zeolitic imidazolate framework-8 and polyacrylamide hydrogel microsphere, which simultaneously transports indole-3-acetic acid and horseradish peroxidase in a single carrier while preventing the premature activation of indole-3-acetic acid. The ATP-responsive characteristic of zeolitic imidazolate framework-8 allows the prodrug system to be activated by the ATP secreted by bacteria to generate reactive oxygen species (ROS), displaying exceptional broad-spectrum antimicrobial ability. Upon disruption of the bacterial membrane by ROS, the leaked intracellular ATP from dead bacteria can accelerate the activation of the prodrug system to further enhance antibacterial efficiency. In vivo experiments in a mouse model demonstrates the applicability of the prodrug system for wound disinfection with minimal side effects.
Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor ...4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.
Mesenchymal stem cells (MSCs) are promising cell sources for regenerative medicine. Growing evidence has indicated that mechanical stimuli are crucial for their lineage-specific differentiation. ...However, the effect of mechanical loading on redox balance and the intracellular antioxidant system in MSCs was unknown. In this study, human bone marrow-derived MSCs (BM-MSCs) were subjected to cyclic stretch at the magnitude of 2.5%, 5%, and 10%. Cell proliferation, intracellular reactive oxygen species (ROS), expression of antioxidant enzymes, and osteogenic differentiation were evaluated. RNA was extracted and subjected to DNA microarray analysis. Sirtinol and compound C were used to investigate the underlying mechanisms involved silent information regulator type 1 (SIRT1) and AMP-activated protein kinase (AMPK). Our results showed that mechanical stretch at appropriate magnitudes increased cell proliferation, up-regulated extracellular matrix organization, and down-regulated matrix disassembly. After 3 days of stretch, intracellular ROS in BM-MSCs were decreased but the levels of antioxidant enzymes, especially superoxide dismutase 1 (SOD1), were up-regulated. Osteogenesis was improved by 5% stretch rather than 10% stretch, as evidenced by increased matrix mineralization and osteogenic marker gene expression. The expression of SIRT1 and phosphorylation of AMPK were enhanced by mechanical stretch; however, inhibition of SIRT1 or AMPK abrogated the stretch-induced antioxidant effect on BM-MSCs and inhibited the stretch-mediated osteogenic differentiation. Our findings reveal that mechanical stretch induced antioxidant responses, attenuated intracellular ROS, and improved osteogenesis of BM-MSCs. The stretch-induced antioxidant effect was through activation of the AMPK-SIRT1 signaling pathway. Our findings demonstrated that appropriate mechanical stimulation can improve MSC antioxidant functions and benefit bone regeneration.
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•Mechanical stretch induces antioxidant responses in BM-MSCs.•Intracellular ROS formation is attenuated by cyclic stretch.•Stretch-mediated antioxidant effect is via activation of AMPK and SIRT1.•Appropriate stretch promotes osteogenic differentiation of BM-MSCs.•Excessive stretch has an adverse effect on cellular antioxidant system.
In this research, low modulus carbon fiber (CF)-reinforced polyetheretherketone composite plates (CF-PEEK plates) were compared with traditional metal plates using finite element analysis to ...establish a reference for clinical application.
Plates of stainless steel, titanium alloy (Ti6Al4V), or CF-PEEK with different carbon fiber reinforcement ratios (CF30, CF50, and CF60) were used to fix the tibial shaft comminuted fracture. The maximum stress, the maximum displacement of fracture and the stress shielding of cortex bone were analyzed.
Under 200 N axial compression, the maximum displacement was measured in the CF30 plate (4.62 mm) and the minimum in the stainless steel plate (0.23 mm). The stress shielding rates of stainless steel, titanium, CF30, CF50, and CF60 plates were 59.4%, 54.4%, 23.75%, 48.75% and 66.25%. Under 700 N axial compression, the internal fixation by the CF30 plate failed. Among the other 4 plates, the maximum displacement was measured in the CF50 plate (2.52 mm) and the minimum in the stainless steel plate (0.78 mm). The stress shielding rate of plates made of stainless steel, titanium, CF50, and CF60 were 57.1%, 52.0%, 48.1%, and 67.8%.
CF50 plates can be safely used in the tibial shaft comminuted fracture. The micromotion in the CF50 and CF60 plate was more beneficial to callus formation and fracture healing. The stress shielding of the cortex bone under the CF50 plate was the lowest. The finite element analysis indicated that the CF-PEEK material is worthy of further study because of its biomechanical advantages.
IntroductionApproximately 17.5% of couples of reproductive age have experienced infertility. Women with a poor ovarian response (POR) must undergo in vitro fertilisation (IVF) and embryo transfer to ...achieve pregnancy. However, studies have reported a poor response to gonadotropin stimulation in women undergoing IVF-ET. Results from animal experiments suggest that granulocyte colony-stimulating factor (G-CSF) has a curative effect by protecting ovarian function, reducing follicle loss and delaying premature ovarian failure in rats caused by chemotherapy. Clinical studies on the therapeutic effect of G-CSF are deficient; therefore, this study will investigate its ability to improve ovum quality and maturity among women with POR undergoing IVF/intracytoplasmic sperm injection (ICSI).Methods and analysisThis clinical, multicentre, triple-blind, placebo-controlled trial will employ balanced randomisation (1:1). The planned sample size is 312 participants (156 subjects in each group). A total of 312 patients with infertility undergoing IVF/ICSI will be recruited from four public hospitals in China. The participants will be randomly divided into an experimental group (G-CSF) and a placebo group (control). All patients will be treated by using the progestin-primed ovarian stimulation superovulation protocol. The primary outcome will be D3 embryo quality. The number of ova obtained, MII ova and transferable embryos will be inclusive in the secondary outcome.Ethics and disseminationTo our knowledge, this is the first clinical trial to investigate the effect of G-CSF treatment timing and stimulation protocol in patients with POR in China. This study will provide new information about G-CSF efficacy among patients with POR undergoing IVF/ICSI and can help improve ovum quality and maturity. Clinical trials on this subject are deficient in China; therefore, a well-designed randomised trial is needed to determine the ability of G-CSF to improve ovum quality and maturity to facilitate conception among women with POR treated with IVF/ICSI.Trial registration numberChiCTR2200062412.
Douchi is a type of traditional Chinese flavoring food that has been used for thousands of years and is produced by multispecies solid-state fermentation. However, the correlation between the flavor, ...the microbiota, and the functional core microbiota in Aspergillus-type douchi fermentation remains unclear. In this study, Illumina MiSeq sequencing and chromatography were used to investigate the bacterial community and flavor components in Aspergillus-type douchi fermentation. The dominant phyla were Firmicutes, Proteobacteria, and Actinobacteria, and the dominant genera were Weissella, Bacillus, Anaerosalibacter, Lactobacillus, Staphylococcus, and Enterococcus. A total of 58 flavor components were detected during fermentation, including two alcohols, 14 esters, five pyrazines, three alkanes, four aldehydes, three phenols, six acids, and five other compounds. Bidirectional orthogonal partial least square modeling showed that Corynebacterium_1, Lactococcus, Atopostipes, Peptostreptococcus, norank_o__AKYG1722, Truepera, Gulosibacter, norank_f__Actinomycetaceae, and unclassified_f__Rhodobacteraceae are the functional core microbiota responsible for the formation of the flavor components during douchi fermentation. This is the first study to investigate the functional core microbiota in douchi fermentation using Illumina MiSeq sequencing and chromatographic techniques. Our findings extend our understanding of the relationships between flavor, the microbiota, and the functional core microbiota during Aspergillus-type douchi fermentation.
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