MSCs are used for treatment of inflammatory conditions or for regenerative purposes. MSCs are complete cells and allogenic transplantation is in principle possible, but mostly autologous use is preferred. In recent years, it was discovered that cells secrete extracellular vesicles. These are active budded off vesicles that carry a cargo. The cargo can be miRNA, protein, lipids etc. The extracellular vesicles can be transported through the body and fuse with target cells. Thereby, they influence the phenotype and modulate the disease. The extracellular vesicles have, like the MSCs, immunomodulatory or regenerative capacities. This review will focus on those features of extracellular vesicles and discuss their dual role. Besides the immunomodulation, the regeneration will concentrate on bone, cartilage, tendon, vessels and nerves. Current clinical trials with extracellular vesicles for immunomodulation and regeneration that started in the last five years are highlighted as well. In summary, extracellular vesicles have a great potential as disease modulating entity and treatment. Their dual characteristics need to be taken into account and often are both important for having the best effect. 

Extracellular vesicles are key players in mesenchymal stem cells' dual potential to regenerate and modulate the immune system.

Abstract Background Numerous investigations have suggested links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs), but causality has not been proven. This study used Mendelian randomization (MR) to investigate the causal associations between 91 CIPs and cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), spinal canal stenosis (SCS), and spondylolisthesis/spondylolysis. Methods Genetic variants data for CIPs and SDDs were obtained from the genome‐wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary method, analyzing the validity and robustness of the results through pleiotropy and heterogeneity tests and performing reverse MR analysis to test for reverse causality. Results The IVW results with Bonferroni correction indicated that beta‐nerve growth factor (β‐NGF), C‐X‐C motif chemokine 6 (CXCL6), and interleukin‐6 (IL‐6) can increase the risk of CS. Fibroblast growth factor 19 (FGF19), sulfotransferase 1A1 (SULT1A1), and tumor necrosis factor‐beta (TNF‐β) can increase PD/SD risk, whereas urokinase‐type plasminogen activator (u‐PA) can decrease the risk of PD/SD. FGF19 and TNF can increase SCS risk. STAM binding protein (STAMBP) and T‐cell surface glycoprotein CD6 isoform (CD6 isoform) can increase the risk of spondylolisthesis/spondylolysis, whereas monocyte chemoattractant protein 2 (MCP2) and latency‐associated peptide transforming growth factor beta 1 (LAP‐TGF‐β1) can decrease spondylolisthesis/spondylolysis risk. Conclusions MR analysis indicated the causal associations between multiple genetically predicted CIPs and the risk of four SDDs (CS, PD/SD, SCS, and spondylolisthesis/spondylolysis). This study provides reliable genetic evidence for in‐depth exploration of the involvement of CIPs in the pathogenic mechanism of SDDs and provides novel potential targets for SDDs. 

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study

Bee venom acupuncture, a type of herbal acupuncture, combines the pharmacological actions of bioactive compounds from bee venom with the mechanical stimulation of meridian points. Bee venom acupuncture is gaining popularity, particularly in the Republic of Korea, primarily for pain relief of various conditions. This study aimed to summarize and evaluate the available evidence on the use of bee venom acupuncture for recovery after bone fractures. Electronic literature searches for experimental studies and clinical trials were conducted using the PubMed, China Academic Journals (CAJ), and OASIS databases. The search revealed 31 studies, of which six met our criteria. These studies demonstrated that bee venom acupuncture can be effective in treating bone fractures, suggesting a promising area for future research. However, evidence supporting its efficacy in this context is limited. Rigorous trials with large sample sizes and robust designs are needed to clarify the role of bee venom acupuncture for these indications. In addition, future studies should explore the optimal dosage and concentration of bee venom acupuncture. 

Clinical Effectiveness of Bee Venom Acupuncture for Bone Fractures and Potential Mechanisms: A Narrative Overview

Stem Cells in Orthopaedics and Sports Injuries: A Comprehensive Review and Future Research Directions

Would Exosome Therapy be Effective for Bone Regeneration? Systematic Review and Meta-Analysis

Bone fracture repair is a multiphased regenerative process requiring paracrine intervention throughout the healing process. Mesenchymal stem cells (MSCs) play a crucial role in cell-to-cell communication and the regeneration of tissue, but their transplantation is difficult to regulate. The paracrine processes that occur in MSC-derived extracellular vesicles (MSC-EVs) have been exploited for this study. The primary goal was to determine whether EVs secreted by TGF-β1-stimulated MSCs (MSCTGF-β1-EVs) exhibit greater effects on bone fracture healing than EVs secreted by PBS-treated MSCs (MSCPBS-EVs). Our research was conducted using an in vivo bone fracture model and in vitro experiments, which included assays to measure cell proliferation, migration, and angiogenesis, as well as in vivo and in vitro gain/loss of function studies. In this study, we were able to confirm that SCD1 expression and MSC-EVs can be induced by TGF-β1. After MSCTGF-β1-EVs are transplanted in mice, bone fracture repair is accelerated. MSCTGF-β1-EV administration stimulates human umbilical vein endothelial cell (HUVEC) angiogenesis, proliferation, and migration in vitro. Furthermore, we were able to demonstrate that SCD1 plays a functional role in the process of MSCTGF-β1-EV-mediated bone fracture healing and HUVEC angiogenesis, proliferation, and migration. Additionally, using a luciferase reporter assay and chromatin immunoprecipitation studies, we discovered that SREBP-1 targets the promoter of the SCD1 gene specifically. We also discovered that the EV-SCD1 protein could stimulate proliferation, angiogenesis, and migration in HUVECs through interactions with LRP5. Our findings provide evidence of a mechanism whereby MSCTGF-β1-EVs enhance bone fracture repair by regulating the expression of SCD1. The use of TGF-β1 preconditioning has the potential to maximize the therapeutic effects of MSC-EVs in the treatment of bone fractures.

/pdf/extracellular-vesicles-secreted-by-tgf-b1-treated-21frjl2g.pdf

Extracellular Vesicles Secreted by TGF-β1-Treated Mesenchymal Stem Cells Promote Fracture Healing by SCD1-Regulated Transference of LRP5

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Extracellular Vesicles Secreted by TGF-β1-Treated Mesenchymal Stem Cells Promote Fracture Healing by SCD1-Regulated Transference of LRP5