MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. / MiR-4465修饰的间质干细胞来源的小细胞外囊泡通过靶向LOXL2表达抑制肝纤维化的进展.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.

Mesenchymal stem cell therapy using Pal-KTTKS-enriched carboxylated cellulose improves burn wound in rat model.

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. / MiR-4465修饰的间质干细胞来源的小细胞外囊泡通过靶向LOXL2表达抑制肝纤维化的进展.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

The exo-microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs).

A major factor in long-term impairment is stroke. Patients with persistent stroke and severe functional disabilities have few therapy choices. Long noncoding RNAs (lncRNAs) may contribute to the regulation of the pathophysiologic processes of ischemic stroke as shown by altered expression of lncRNAs and microRNA (miRNAs) in blood samples of acute ischemic stroke patients. On the other hand, multipotent mesenchymal stem cells (MSCs) increase neurogenesis, and angiogenesis, dampen neuroinflammation, and boost brain plasticity to improve functional recovery in experimental stroke models. MSCs can be procured from various sources such as the bone marrow, adipose tissue, and peripheral blood. Under the proper circumstances, MSCs can differentiate into a variety of mature cells, including neurons, astrocytes, and oligodendrocytes. Accordingly, the capability of MSCs to exert neuroprotection and also neurogenesis has recently attracted more attention. Nowadays, lncRNAs and miRNAs derived from MSCs have opened new avenues to alleviate stroke symptoms. Accordingly, in this review article, we examined various studies concerning the lncRNAs and miRNAs' role in stroke pathogenesis and delivered an overview of the therapeutic role of MSC-derived miRNAs and lncRNAs in stroke conditions.

Adipose-derived mesenchymal stem cells (MSCs) are a superior cell source for bone tissue engineering.

Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors, osteoinductive biofactors and biocompatible scaffold materials. Mesenchymal stem cells (MSCs) represent the most promising seed cells for bone tissue engineering. As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat, MSCs can be isolated from numerous tissues and exhibit varied differentiation potential. To identify an optimal progenitor cell source for bone tissue engineering, we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources, including immortalized mouse embryonic fibroblasts (iMEF), immortalized mouse bone marrow stromal stem cells (imBMSC), immortalized mouse calvarial mesenchymal progenitors (iCAL), and immortalized mouse adipose-derived mesenchymal stem cells (iMAD). We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro, whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair. Transcriptomic analysis revealed that, while each MSC line regulated a distinct set of target genes upon BMP9 stimulation, all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt, TGF-ß, PI3K/AKT, MAPK, Hippo and JAK-STAT pathways. Collectively, our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.

Stem Cell-Based Tissue Engineering Approaches for Diabetic Foot Ulcer: a Review from Mechanism to Clinical Trial.

Diabetic foot ulcer (DFU) is a complication from incomplete or prolonged wound healing, at times requires amputation, putting substantial health and socioeconomic burden. Wound healing is a dynamic overlapping process that can be regulated by arrays of molecular factors showing redundancy in function. However, dysregulation in the mechanism of angiogenesis, extra cellular matrix (ECM) formation and immune modulation are the major causes for impair wound healing in hyperglycaemic patients. Despite development of wound care research, there is a lack of well-accepted targeted therapy with multidisciplinary approach for DFU treatment. Stem cell therapy holds a promising outcome both in preclinical and clinical trials because of its ability to promote healing via regeneration and specialized tissue differentiation. Among different types of stem cells, regenerative potential of mesenchymal stem cell (MSC) is well demonstrated in both experimental and clinical trial. Still there is a huge knowledge gap among medical practitioners for deciding the best stem cell source, administration route, and safety. This review strengthens the fact that why stem cell therapy is a promising candidate to treat DFU and cited multiple tissue engineering and biomaterial-based approaches for delivering stem cells and their aftermath paracrine events. Based on the pre-clinical and clinical studies, the review tried to come up with optimum stem cell source and delivery route for the treatment of DFU. At last, the review glances on possible direction to enhance therapeutics strategy for the same, including different approaches like: phytocompounds, exosomes, scaffold geometry, cell preconditioning and licensing etc.

Intracerebral Transplantation of Autologous Mesenchymal Stem Cells Improves Functional Recovery in a Rat Model of Chronic Ischemic Stroke.

While treatments exist for the acute phase of stroke, there are limited options for patients with chronic infarcts and long-term disability. Allogenic mesenchymal stem cells (alloMSCs) show promise for the treatment of stroke soon after ischemic injury. There is, however, no information on the use of autologous MSCs (autoMSCs), delivered intracerebrally in rats with a chronic infarct. In this study, rats underwent middle cerebral artery occlusion (MCAO) to induce stroke followed by bone marrow aspiration and MSC expansion in a closed bioreactor. Four weeks later, brain MRI was obtained and autoMSCs (1 × 106, 2.5 × 106 or 5 × 106; n = 6 each) were stereotactically injected into the peri-infarct and compared to controls (MCAO only; MCAO + PBS; n = 6-9). Behavior was assessed using the modified neurological severity score (mNSS). For comparison, an additional cohort of MCAO rats were implanted with 2.5 × 106 alloMSCs generated from a healthy rat. All doses of autoMSCs produced significant improvement (54-70%) in sensorimotor function 60 days later. In contrast, alloMSCs improved only 31.7%, similar to that in PBS controls 30%. Quantum dot-labeled auto/alloMSCs were found exclusively at the implantation site throughout the post-transplantation period with no tumor formation on MRI or Ki67 staining of engrafted MSCs. Small differences in stroke volume and no differences in corpus callosum width were observed after MSC treatment. Stroke-induced glial reactivity in the peri-infarct was long-lasting and unabated by auto/alloMSC transplantation. These studies suggest that intracerebral transplantation of autoMSCs as compared to alloMSCs may be a promising treatment in chronic stroke.

Exosomes derived from mesenchymal stromal cells exert a therapeutic effect on hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway.

OBJECTIVE: Hypoxic pulmonary hypertension (HPH) is a progressive and life-threatening disease characterized by perivascular inflammation, pulmonary vascular remodeling, and occlusion. Mesenchymal stromal cell-derived exosomes (MSC-exo) have emerged as potential therapeutic agents due to their role in cell communication and the transportation of bioactive molecules. In this study, we aimed to investigate the therapeutic effects of MSC-exo against HPH and elucidate the underlying molecular mechanism. METHODS: Exosomes were isolated from conditioned media of human bone mesenchymal stromal cells using ultracentrifugation and characterized through western blotting, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). An HPH animal model was established in male SD rats, and MSC-exo or phosphate-buffered saline (PBS) were administered via the tail vein for three weeks. Subsequently, right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and pulmonary vascular remodeling were evaluated. Lung tissues from HPH rats and normal rats underwent high-throughput sequencing and transcriptomic analysis. Gene Ontology (GO) analysis was employed to identify upregulated differentially expressed genes. Additionally, rat pulmonary artery smooth muscle cells (PASMC) exposed to platelet-derived growth factor-BB (PDGF-BB) were used to simulate HPH-related pathological behavior. In vitro cellular models were established to examine the molecular mechanism of MSC-exo in HPH. RESULTS: MSC-exo administration protected rats from hypoxia-induced increases in RVSP, RVHI, and pulmonary vascular remodeling. Additionally, MSC-exo alleviated PDGF-BB-induced proliferation and migration of PASMC. Transcriptomic analysis revealed 267 upregulated genes in lung tissues of HPH rats compared to control rats. Gene Ontology analysis indicated significant differences in pathways associated with Yes Associated Protein 1 (YAP1), a key regulator of cell proliferation and organ size. RT-qPCR and western blot analysis confirmed significantly increased expression of YAP1 in HPH lung tissues and PASMC, which was inhibited by MSC-exo treatment. Furthermore, analysis of datasets demonstrated that Secreted Phosphoprotein 1 (SPP1), also known as Osteopontin (OPN), is a downstream binding protein of YAP1 and can be upregulated by PDGF-BB. MSC-exo treatment reduced the expression of both YAP1 and SPP1. Lentivirus-mediated knockdown of YAP1 inhibited PDGF-BB-induced PASMC proliferation, migration, and SPP1 protein levels. CONCLUSION: Our findings demonstrate that MSC-exo exert a therapeutic effect against hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway. The inhibition of YAP1 and downstream SPP1 expression by MSC-exo may contribute to the attenuation of pulmonary vascular remodeling and PASMC proliferation and migration. These results suggest that MSC-exo could serve as a potential therapeutic strategy for the treatment of HPH. Further investigations are warranted to explore the clinical applicability of MSC-exo-based therapies in HPH patients.

Differential Expression of MicroRNA (MiR-27, MiR-145) among Dental Pulp Stem Cells (DPSCs) Following Neurogenic Differentiation Stimuli.

This study sought to evaluate the expression of previously identified microRNAs known to regulate neuronal differentiation in mesenchymal stem cells (MSCs), including miR-27, miR-125, miR-128, miR-135, miR-140, miR-145, miR-218 and miR-410, among dental pulp stem cells (DPSCs) under conditions demonstrated to induce neuronal differentiation. Using an approved protocol, n = 12 DPSCs were identified from an existing biorepository and treated with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), which were previously demonstrated to induce neural differentiation markers including Sox1, Pax6 and NFM among these DPSCs. This study revealed that some microRNAs involved in the neuronal differentiation of MSCs were also differentially expressed among the DPSCs, including miR-27 and miR-145. In addition, this study also revealed that administration of bFGF and EGF was sufficient to modulate miR-27 and miR-145 expression in all of the stimulus-responsive DPSCs but not among all of the non-responsive DPSCs-suggesting that further investigation of the downstream targets of these microRNAs may be needed to fully evaluate and understand these observations.

Mesenchymal stem cell-derived exosomes for managing graft-versus-host disease: An updated view.

Graft-versus-host disease (GvHD) is the most common complication after stem cell transplantation, and also it is one of the primary limiting factors for the use of hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic cancers. GvHD, a systemic inflammatory disease, is caused by donor T cells recognizing the recipient's foreign antigens. In addition, an immune dysregulation, caused by autoreactive immune cells, complicates potent inflammatory process following HSCT. While there is no one approved treatment method for GvHD, corticosteroids are the most common first-line treatment. Exosomes are biological vesicles between 30 and 120 nm in diameter, which carry various biologically active molecules. They are known to play a key role in the paracrine effect of mesenchymal stem cells with therapeutic and tissue repair effects, including an immunosuppressive potential. Exosomes are unable to replicate themselves but because of their small size and fluid-like structure, they can pass through physiological barriers. Exosome are relatively easy to prepare and they can be quickly sterilized by a filtration process. Administration of exosomes, derived from mesenchymal stem cells, effectively reduced GvHD symptoms and significantly increased HSCT recipients' survival. Mesenchymal stem cell-derived exosome therapy reduced clinical symptoms of GvHD in patients after HSCT. Studies in patients with GvHD described that that mesenchymal stem cell-derived exosomes inhibited the release of IFN-γ and TNF-α by activated natural killer (NK cells), thereby reducing the lethal function of NK cells and inflammatory responses. Current review provides a comprehensive overview about the use of mesenchymal stem cells and their derived exosomes for the treatment of GvHD.

Intra-operative Guidelines for the Prevention of Uterine Niche Formation in Cesarean Sections: A Review.

Formation of a uterine niche following a C-section can predispose the patient to future obstetric complications such as dehiscence, uterine rupture, ectopic pregnancy, and placenta accreta. The significant morbidity and mortality of these complications along with increasing C-section rates emphasizes the importance of prevention. However, there are no clear guidelines on intra-operative protocol to prevent postpartum niche formation. Besides surgical technique, the novel use of platelet-rich plasma (PRP) and mesenchymal stem cell (MSC) injections has demonstrated promising potential and may have applications in hysterotomy closures. The objective is to examine current research on optimal C-section procedures to prevent uterine niche formation and subsequent obstetric complications. A systematic review was conducted using PubMed and Google Scholar. Initial searches yielded 827 results. Inclusion criteria were human, animal, and in-vitro studies, peer-reviewed sources, and outcomes pertinent to the uterine niche. Exclusion criteria applied to articles with outcomes unrelated to myometrium and interventions outside of the intra-operative and immediate pre-/post-operative period. Based on the criteria, 41 articles were cited. Pathophysiology of uterine niche formation was associated with incisions through cervical tissue, adhesion formation, and poor approximation. Significant risk factors were low uterine incisions, advanced cervical dilatation, low station, non-closure of the peritoneum, and creation of a bladder flap. There was no consensus on uterine closure as it likely depends on surgical proficiency with the given technique, but a double-layered non-locking suture appears reliable to reduce niche severity. Recent trials indicate that intra-operative PRP/MSC injections may decrease niche incidence and severity, but more research is needed. If prevention or minimization of uterine niche is desired, the optimal C-section protocol should avoid low uterine incisions, choose uterine closure technique based on the surgeon's proficiency (double-layered non-locking is reliable), and close the peritoneum, and myometrial injection of PRP/MSC may be a useful adjunct intervention pending further clinical evidence.

New insights in application of mesenchymal stem cells therapy in tumor microenvironment: pros and cons.

Multipotent mesenchymal stem cells (MSCs) are widely accepted as a useful tool for cell-based therapy of various diseases including malignancies. The therapeutic effects of MSCs are mainly attributed to their immunomodulatory and immunosuppressive properties. Despite the promising outcomes of MSCs in cancer therapy, a growing body of evidence implies that MSCs also show tumorigenic properties in the tumor microenvironment (TME), which might lead to tumor induction and progression. Owing to the broad-spectrum applications of MSCs, this challenge needs to be tackled so that they can be safely utilized in clinical practice. Herein, we review the diverse activities of MSCs in TME and highlight the potential methods to convert their protumorigenic characteristics into onco-suppressive effects.

Exosomes as a Nano-Carrier for Chemotherapeutics: A New Era of Oncology.

Despite the considerable advancements in oncology, cancer remains one of the leading causes of death worldwide. Drug resistance mechanisms acquired by cancer cells and inefficient drug delivery limit the therapeutic efficacy of available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because exosomes have better organotropism, homing capacity, cellular uptake, and cargo release ability than synthetic NDCs. In addition, exosomes can serve as NDCs for both hydrophilic and hydrophobic chemotherapeutic drugs. Thus, this review aimed to summarize the latest advances in cell-free therapy, describing how the exosomes can contribute to each step of the carcinogenesis process and discussing how these nanosized vesicles could be explored as nano-drug carriers for chemotherapeutics.

The microRNAs (miRs) overexpressing mesenchymal stem cells (MSCs) therapy in neurological disorders; hope or hype.

Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. One of the biggest concerns within gene-based therapy is the delivery of the therapeutic microRNAs to the intended place, which is obligated to surpass the biological barriers without undergoing degradation in the bloodstream or renal excretion. Hence, the delivery of modified and unmodified miRNA molecules using excellent vehicles is required. In this light, mesenchymal stem cells (MSCs) have attracted increasing attention. The MSCs can be genetically modified to express or overexpress a particular microRNA aimed with promote neurogenesis and neuroprotection. The current review has focused on the therapeutic capabilities of microRNAs-overexpressing MSCs to ameliorate functional deficits in neurological conditions.

TMT-based quantitative proteomic analysis revealed that FBLN2 and NPR3 are involved in the early osteogenic differentiation of mesenchymal stem cells (MSCs).

The delicate equilibrium between osteoblast and adipocyte differentiation of MSCs is highly regulated. We screened for early-stage osteogenesis- or adipogenesis-based MSCs protein expression profiles using TMT-based quantitative proteomic analysis to identify novel participating molecules. Protein annotation, hierarchical clustering, functional stratification, and protein-protein association assessments were performed. Moreover, two upregulated proteins, namely, FBLN2 and NPR3, were validated to participate in the osteogenic differentiation process of MSCs. After that, we independently downregulated FBLN2 and NPR3 over seven days of osteogenic differentiation, and we performed quantitative proteomics analysis to determine how different proteins were regulated in knockdown vs. control cells. Based on gene ontology (GO) and network analyses, FBLN2 deficiency induced functional alterations associated with biological regulation and stimulus-response, whereas NPR3 deficiency induced functional alterations related to cellular and metabolic processes, and so on. These findings suggested that proteomics remains a useful method for an in-depth study of the MSCs differentiation process. This will assist in comprehensively evaluating its role in osteoporosis and provide additional approaches for identifying as-yet-unidentified effector molecules.

Effect and mechanism of acupuncture on endogenous and exogenous stem cells in disease treatment: A therapeutic review.

Acupuncture is effective intervention, particularly in nerve, endocrine diseases and immune diseases. The potential mechanisms mediating the effects of acupuncture include anti-inflammatory and oxidative stress, inhibition of cell apoptosis, and stimulation of the proliferation and differentiation of endogenous stem cells. Traditional Chinese medicine combined with stem cell transplantation have a synergistic effect in the treatment of diseases. Increasing studies have found that acupuncture can promote the proliferation, differentiation, homing and survival of exogenous stem cells. This article reviews the mechanism of acupuncture and Chinese herbs on endogenous stem cells and exogenous stem cells in the combined intervention of diverse disorders and the major problems in past 15 years, which will provide a reference for future clinical research.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.