ALPL regulates pro-angiogenic capacity of mesenchymal stem cells through ATP-P2X7 axis controlled exosomes secretion DOI Creative Commons
Jiayi Dong,

Wanmin Zhao,

Jiangdong Zhao

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 12, 2024

Abstract Background Early-onset bone dysplasia is a common manifestation of hypophosphatasia (HPP), an autosomal inherited disease caused by ALPL mutation. ablation induces prototypical premature ageing characteristics, resulting in impaired osteogenic differentiation capacity human marrow mesenchymal stem cells (hBMMSCs). As angiogenesis tightly coupled with osteogenesis, it also plays necessary role sustaining homeostasis. We have previously observed decrease expression marker gene CD31 the metaphysis long Alpl +/− mice. However, regulation has remained largely unknown. Methods Exosomes derived from Normal and HPP hBMMSCs were isolated identified ultracentrifugation, transmission electron microscopy, nanoparticle size measurement. The effects on angiogenic patients assessed immunofluorescence, tube formation, wound healing migration assay. exo-ELISA Western Blot used to evaluate exosomes secretion HPP, protein VEGF, PDGFBB, Angiostatin Endostatin respectively. Results verified that resulted pro-angiogenic hBMMSCs, accounting for reduced formation umbilical vein endothelial cells, as quantities proteins composition varied expression. Mechanistically, loss function enhanced ATP release. Additional ATP, turn, led markedly elevated level receptor P2X7, which consequently promoted secretion, decreased promote angiogenesis. Conversely, inhibition P2X7 increased induction preventing excessive release anti-angiogenic deficient-hBMMSCs. Conclusion ALPL–ATP axis regulates ability controlling through receptor. Thus, may be proved effective therapeutic target accelerating neovascularization ALPL–deficient defects.

Язык: Английский

Application of stem cells in regeneration medicine DOI Creative Commons
Ye Jin, Shuangyang Li,

Qixuan Yu

и другие.

MedComm, Год журнала: 2023, Номер 4(4)

Опубликована: Июнь 17, 2023

Abstract Regeneration is a complex process affected by many elements independent or combined, including inflammation, proliferation, and tissue remodeling. Stem cells class of primitive with the potentiality differentiation, regenerate self‐replication, multidirectional immunomodulatory functions. their cytokines not only inextricably linked to regeneration ectodermal skin tissues, but also can be used for treatment variety chronic wounds. produce exosomes in paracrine manner. cell play an important role regeneration, repair, accelerated wound healing, biological properties which are similar stem cells, while safer more effective. Skin bone tissues critical organs body, essential sustaining life activities. The weak repairing ability leads pronounced impact on quality patients, could alleviated treatment. However, there obstacles that trough improved bioavailability. This paper summarizes applications mechanisms healing. We propose new ways utilizing through different nanoformulations, liposomes nanoliposomes, polymer micelles, microspheres, hydrogels, scaffold microneedles, improve use healing regeneration.

Язык: Английский

Процитировано

57

Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models DOI Open Access
Ornella Urzì, Roberta Gasparro, Elisa Costanzo

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12046 - 12046

Опубликована: Июль 27, 2023

Although historically, the traditional bidimensional in vitro cell system has been widely used research, providing much fundamental information regarding cellular functions and signaling pathways as well nuclear activities, simplicity of this does not fully reflect heterogeneity complexity vivo systems. From arises need to use animals for experimental research testing. Nevertheless, animal experimentation presents various aspects complexity, such ethical issues, which led Russell Burch 1959 formulate 3R (Replacement, Reduction, Refinement) principle, underlying urgent introduce non-animal-based methods research. Considering this, three-dimensional (3D) models emerged scientific community a bridge between models, allowing achievement differentiation while avoiding The purpose review is provide general overview most common establish 3D culture discuss their promising applications. Three-dimensional cultures have employed study both organ physiology diseases; moreover, they represent valuable tool studying many cancer. Finally, possibility using drug screening regenerative medicine paves way development new therapeutic opportunities diseases.

Язык: Английский

Процитировано

48

Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration DOI Open Access

Bárbara Torrecillas-Baena,

Victoria Pulido-Escribano,

Gabriel Dorado

и другие.

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(13), С. 4385 - 4385

Опубликована: Июнь 29, 2023

Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, traumatic fractures require effective treatments that favor bone formation regeneration. Among these, cell therapy based on mesenchymal cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part paracrine properties. These mainly mediated extracellular vesicle (EV) secretion. EV modulates processes inflammation, angiogenesis, proliferation, migration, differentiation. Thus, MSC-EV currently an important tool for the development of cell-free therapies medicine. This review describes current knowledge effects different phases used intravenous injection, directly or combination with types biomaterials, preclinical models diseases. They have shown great clinical potential medicine applied to bone. findings should be confirmed through standardization protocols, a better understanding mechanisms action, appropriate trials. All will allow translation human clinic applications.

Язык: Английский

Процитировано

26

The application of extracellular vesicles in orthopedic diseases DOI Creative Commons
Yuexin Li, Haiyan Zhang, Yu Jiang

и другие.

Deleted Journal, Год журнала: 2024, Номер 2(3)

Опубликована: Март 13, 2024

Abstract Orthopedic diseases, such as osteoarthritis and fractures, place a significant burden on individuals healthcare systems worldwide. Extracellular vesicles (EVs), which are membrane‐derived particles, have emerged novel tool in the field of orthopedics. EVs play crucial role diagnosing, regenerating, treating orthopedic diseases. In terms diagnosis, serve potential biomarkers, carrying unique donor cell information circulating effectively bodily fluids. Specific biomolecules within EVs, including proteins, nucleic acids, microRNAs, hold promise biological markers for early detection monitoring shown promoting bone cartilage regeneration. They can enhance tissue regeneration by stimulating various stem cells to proliferate, migrate, differentiate into mature chondrocytes osteocytes. also target specific tissues, making them attractive candidates drug delivery efficiently deliver therapeutic cargo, anti‐inflammatory agents growth factors, affected sites, enhancing treatment efficacy while minimizing toxicity adverse effects. conclusion,

Язык: Английский

Процитировано

14

Extracellular vesicles are key players in mesenchymal stem cells’ dual potential to regenerate and modulate the immune system DOI Creative Commons
Martijn van Griensven, Elizabeth R. Balmayor

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115203 - 115203

Опубликована: Фев. 9, 2024

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

Язык: Английский

Процитировано

13

Quercetin‐Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects DOI Creative Commons

Huimin Zhu,

Chao Cai,

Yeke Yu

и другие.

Advanced Science, Год журнала: 2024, Номер 11(29)

Опубликована: Май 15, 2024

Abstract Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, is closely related to the occurrence progression of various systemic diseases. However, elucidating processes periodontal promoting bone regeneration remains a challenge. Here, quercetin demonstrated reduce oxidative stress state orofacial mesenchymal stem cells (OMSCs) in vitro affect osteogenic growth OMSCs through molecular mechanisms that mediate m6A change Per1. Nevertheless, limited therapeutic efficacy medication limitations local resulting from small, moist, highly dynamic environment make it challenging treat tissues with medication. Herein, biosafe injectable hydrogel drug‐controlled delivery system constructed as bone‐enhancing factory loaded injury tissues. This drug‐carrying made up nanoscale bioglass microspheres light‐cured hydrogel, allows effective drug particle loading cementation moist environment. Furthermore, demonstrates ability stimulate differentiation Per1‐dependent manner, which ultimately promotes repair, suggesting this has potential for clinical therapy.

Язык: Английский

Процитировано

13

Mesenchymal stem cell-derived extracellular vesicles: a regulator and carrier for targeting bone-related diseases DOI Creative Commons

Jiandong Tang,

Xiangyu Wang, Xu Lin

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Май 2, 2024

Abstract The escalating threat of bone-related diseases poses a significant challenge to human health. Mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs), as inherent cell-secreted natural products, have emerged promising treatments for diseases. Leveraging outstanding features such high biocompatibility, low immunogenicity, superior biological barrier penetration, and extended circulating half-life, MSC-EVs serve potent carriers microRNAs (miRNAs), long no-code RNAs (lncRNAs), other biomolecules. These cargo molecules play pivotal roles in orchestrating bone metabolism vascularity through diverse mechanisms, thereby contributing the amelioration Additionally, engineering modifications enhance bone-targeting ability MSC-EVs, mitigating systemic side effects bolstering their clinical translational potential. This review comprehensively explores mechanisms which regulate disease progression. It delves into therapeutic potential adept drug carriers, augmented by engineered modification strategies tailored osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, osteosarcoma. In conclusion, exceptional promise exhibited positions them an excellent solution with considerable applications orthopedics.

Язык: Английский

Процитировано

10

Signaling pathways activated and regulated by stem cell-derived exosome therapy DOI Creative Commons

Ding Li,

Danni Li, Zhao Wang

и другие.

Cell & Bioscience, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 20, 2024

Stem cell-derived exosomes exert comparable therapeutic effects to those of their parental stem cells without causing immunogenic, tumorigenic, and ethical disadvantages. Their advantages are manifested in the management a broad spectrum diseases, dosing versatility exemplified by systemic administration local delivery. Furthermore, activation regulation various signaling cascades have provided foundation for claimed curative exosomal therapy. Unlike other relevant reviews focusing on upstream aspects (e.g., yield, isolation, modification), downstream (e.g. phenotypic changes, tissue response, cellular behavior) exosome therapy, this unique review endeavors focus affected pathways. After meticulous dissection literature from past five years, we present comprehensive, up-to-date, disease-specific, pathway-oriented review. Exosomes sourced types can regulate major pathways PTEN/PI3K/Akt/mTOR, NF-κB, TGF-β, HIF-1α, Wnt, MAPK, JAK-STAT, Hippo, Notch cascades) minor during treatment numerous diseases encountered orthopedic surgery, neurosurgery, cardiothoracic plastic general specialties. We provide novel perspective future research through bridging gap between surgical indications when designing further preclinical studies clinical trials.

Язык: Английский

Процитировано

6

The Latest Advances in the Use of Nanoparticles in Endodontics DOI Creative Commons
Żaneta Anna Mierzejewska,

Bartłomiej Rusztyn,

Kamila Łukaszuk

и другие.

Applied Sciences, Год журнала: 2024, Номер 14(17), С. 7912 - 7912

Опубликована: Сен. 5, 2024

Recent decades clearly demonstrate the growing use of nanomaterials in medical practice, and their effectiveness is systematically confirmed by consequent scientific research. An example dentistry endodontic treatment, which, due to its specificity, one most demanding procedures, fraught with numerous challenges, such as difficulties reaching tooth roots ineffective cleaning or insufficient sealing root canals, which may lead re-infection damage adjacent structures. The has a positive impact on solving these problems, combination biomaterials nanometric technology makes treatment more effective, precise comfortable for patients, contributes improving quality dental care. Currently, high biocompatibility can be used endodontics components irrigation solutions, rinsing canals drug carriers intracanal use. Nanomaterials are also sealants filling canals. However, latest research shows that reducing size materials “nano” scale significantly affects basic physicochemical properties, leads increased reactivity ability interact at molecular level. These unique have contributed medical-related raise concerns provoke discussions about safety direct contact tissues.

Язык: Английский

Процитировано

6

Hypoxic Preconditional Engineering Small Extracellular Vesicles Promoted Intervertebral Disc Regeneration by Activating Mir‐7‐5p/NF‐Κb/Cxcl2 Axis DOI Creative Commons
Hongxing Hu, Zhaojie Wang, Huiyi Yang

и другие.

Advanced Science, Год журнала: 2023, Номер 10(35)

Опубликована: Окт. 23, 2023

Abstract Chronic low back pain (LBP) caused by intervertebral disc (IVD) degradation is a serious socioeconomic burden that can cause severe disabilities. Addressing the underlying pathogenic mechanisms of IVD degeneration may inspire novel therapeutic strategy for LBP. Herein, hypoxic preconditioning improves both biological function MSCs in hostile microenvironments and enhances production small extracellular vesicles (sEVs) with desirable functions. In vitro results reveal preconditional engineering sEVs (HP‐sEVs) alleviate inflammatory degradation, enhance proliferation nucleus pulposus (NP) cells, promote proteoglycan synthesis collagen formation. Transcriptomic sequencing reveales excellent effects HP‐sEVs promoting matrix regeneration through delivery microRNA(miR)‐7‐5p, which further suppresses p65 thus inhibition Cxcl2 production. Moreover, vivo confirm robust role same mechanism mediated miR‐7‐5p delivery. conclusion, this study provides treating valuable understanding mechanism‐of‐action associated chronic lower pain.

Язык: Английский

Процитировано

13