Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(1), P. 100881 - 100881

Published: Jan. 1, 2023

Systematic bone loss is commonly complicated with inflammatory bowel diseases (IBDs) unclear pathogenesis and uncertain treatment. In experimental colitis mouse models established by dextran sulfate sodium IL-10 knockout induced piroxicam, mass quality are significantly decreased. Colitis mice demonstrate a lower formation rate fewer osteoblasts in femur. Bone marrow mesenchymal stem/stromal cells (BMSCs) from tend to differentiate into adipocytes rather than osteoblasts. Serum patients IBD promotes adipogenesis of human BMSCs. RNA sequencing reveals that downregulates Wnt signaling For treatment, exosomes Golgi glycoprotein 1 inserted could carry agonist accumulate via intravenous administration. They alleviate loss, promote formation, accelerate fracture healing mice. Collectively, BMSC commitment microenvironment contributes quantity be rescued redirecting differentiation toward through bone-targeted drug delivery.

Language: Английский

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Osteoporosis pathogenesis and treatment: existing and emerging avenues

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Sept. 4, 2022

Abstract Osteoporotic fractures lead to increased disability and mortality in the elderly population. With rapid increase aging population around globe, more effective treatments for osteoporosis osteoporotic are urgently required. The underlying molecular mechanisms of believed be due activity osteoclasts, decreased osteoblasts, or both, which leads an imbalance bone remodeling process with accelerated resorption attenuated formation. Currently, available clinical have mostly focused on factors influencing remodeling; however, they their own limitations side effects. Recently, cytokine immunotherapy, gene therapy, stem cell therapy become new approaches treatment various diseases. This article reviews latest research mechanisms, as well how this underpins current potential novel osteoporosis.

Language: Английский

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Extracellular vesicles: a rising star for therapeutics and drug delivery

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 20, 2023

Abstract Extracellular vesicles (EVs) are nano-sized, natural, cell-derived that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve natural carriers for therapeutic agents drugs, have many advantages over conventional nanocarriers, including low immunogenicity, good biocompatibility, blood – brain barrier penetration, capacity gene delivery. This review first introduces classification of EVs then discusses several currently popular methods isolating purifying EVs, EVs-mediated drug delivery, functionalization carriers. Thereby, it provides new avenues development EVs-based strategies in different fields medicine. Finally, highlights some challenges future perspectives with regard to clinical application EVs. Graphical

Language: Английский

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Biomaterial-induced pathway modulation for bone regeneration

Biomaterials, Journal Year: 2022, Volume and Issue: 283, P. 121431 - 121431

Published: Feb. 18, 2022

Embryogenic developmental processes involve a tightly controlled regulation between mechanical forces and biochemical cues such as growth factors, matrix proteins, cytokines. This interplay remains essential in the mature body, with aberrant pathway signaling leading to abnormalities atherosclerosis cardiovascular system, inflammation tendon tissue, or osteoporosis bone. The aim of bone regenerative strategies is develop tools procedures that will harness body's own self-repair ability order successfully regenerate even very large complex defects restore normal function. To achieve this, understanding pathways govern progenitor differentiation towards osteogenic lineages, their phenotypical maintenance, construction functional tissue imperative subsequently therapies mimic these processes. While body literature exists describes how stimuli guide cell behavior culture dish, due lack an appropriate environment, signals are often insufficient inappropriate for achieving desirable response body. Moreover, rarely rely on stimulus, factor alone, instead comprise carrier biomaterial introduces different microenvironment from dish. Therefore, this review, we discuss which biomaterials elicit influence relevant regeneration describe mechanisms behind effects, inspire development novel, more effective therapies.

Language: Английский

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Targeting strategies for bone diseases: signaling pathways and clinical studies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 17, 2023

Abstract Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From initial selective antibody, antitoxin to drug delivery that emerged past decades, more precise therapeutic efficacy is realized specific pathological sites clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone characterized by complex remodeling and homeostatic regulation mechanism, which makes therapy for skeletal diseases challenging than other tissues. Bone-targeted has been considered promising approach handling such drawbacks. With deepening understanding biology, improvements some established bone-targeted drugs novel targets deliveries on horizon. In this review, we provide panoramic summary recent strategies based targeting. We highlight targeting structure biology. For agents, addition classic denosumab, romosozumab, PTH1R ligands, potential process key membrane expressions, cellular crosstalk, gene expression, all cells exploited. delivery, different matrix, marrow, are summarized comparison between ligands. Ultimately, review will summarize translation therapies perspective challenges application clinic future trends area.

Language: Английский

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Advances in materials-based therapeutic strategies against osteoporosis

Biomaterials, Journal Year: 2023, Volume and Issue: 296, P. 122066 - 122066

Published: Feb. 20, 2023

Language: Английский

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Bone‐Targeted Exosomes: Strategies and Applications

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(18)

Published: March 7, 2023

Abstract As the global population ages, bone‐related diseases have increasingly become a major social problem threatening human health. Exosomes, as natural cell products, been used to treat due their superior biocompatibility, biological barrier penetration, and therapeutic effects. Moreover, modified exosomes exhibit strong bone‐targeting capabilities that may improve efficacy avoid systemic side effects, demonstrating promising translational potential. However, review of bone‐targeted is still lacking. Thus, recently developed for applications in this are focused. The biogenesis regulatory functions exosomes, constructive strategies bone‐targeting, effects introduced. By summarizing developments challenges It striven shed light on selection exosome different bone highlight potential future clinical orthopedics.

Language: Английский

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Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease

Theranostics, Journal Year: 2023, Volume and Issue: 13(4), P. 1264 - 1285

Published: Jan. 1, 2023

With the increase of population aging, number Alzheimer's disease (AD) patients is also increasing.According to current estimates, approximately 11% people over 65 suffer from AD, and that percentage rises 42% among 85.However, no effective treatment capable decelerating or stopping AD progression available.Furthermore, AD-targeted drugs composed synthetic molecules pose concerns regarding biodegradation, clearance, immune response, neurotoxicity.Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are essential intercellular communication mediators holding great promise as therapeutics owing their biocompatibility, versatility, effortless storage, superior safety, ability transport messenger noncoding RNAs, proteins, lipids, DNAs, other bioactive compounds derived cells.The functionalisation engineering strategies MSC-EVs highlighted (e.g.preconditioning, drug loading, surface modification, artificial EV fabrication), which could improve by multiple therapeutic effects, including clearing abnormal protein accumulation achieving neuroprotection immunomodulatory effects.Herein, this review summarises state-of-the-art engineer MSC-EVs, discusses progress in use therapeutics, presents perspectives challenges associated with related clinical applications, concludes engineered show immense potential therapy.

Language: Английский

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Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: July 11, 2024

Abstract Exosomes are extracellular vesicles generated by all cells and they carry nucleic acids, proteins, lipids, metabolites. They mediate the exchange of substances between cells,thereby affecting biological properties activities recipient cells. In this review, we briefly discuss composition exocomes exosome isolation. We also review clinical applications exosomes in cancer biology as well strategies exosome-mediated targeted drug delivery systems. Finally, application context therapeutics both practice literature discussed.

Language: Английский

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The role and applications of extracellular vesicles in osteoporosis

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 23, 2024

Abstract Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture, which increases patient susceptibility to fragile fractures. The intricate mechanisms governing homeostasis are substantially impacted extracellular vesicles (EVs), play crucial roles in both pathological physiological contexts. EVs derived from various sources exert distinct effects on osteoporosis. Specifically, released osteoblasts, endothelial cells, myocytes, mesenchymal stem cells contribute formation due their unique cargo proteins, miRNAs, cytokines. Conversely, secreted osteoclasts immune promote resorption inhibit formation. Furthermore, use as therapeutic modalities or biomaterials for diagnosing managing osteoporosis promising. Here, we review current understanding impact homeostasis, including classification biogenesis regulatory present an overview latest research progress treating using EVs. Finally, discuss challenges prospects translational

Language: Английский

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