Can extracellular vesicles be considered as a potential frontier in the treatment of intervertebral disc disease? DOI Creative Commons
S.Y. Zhu, Junlin Wang,

Moran Suo

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102094 - 102094

Published: Oct. 18, 2023

As a global public health problem, low back pain (LBP) caused by intervertebral disc degeneration (IDD) seriously affects patients' quality of life. In addition, the prevalence IDD tends to be younger, which brings huge burden individuals and society economically. Current treatments do not delay or reverse progression IDD. The emergence biologic therapies has brought new hope for treatment Among them, extracellular vesicles (EVs), as nanoscale bioactive substances that mediate cellular communication, have now produced many surprising results in research This article reviews mechanisms roles EVs delaying describes prospects challenges EVs.

Language: Английский

MiR‐17‐5p‐engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21 DOI Creative Commons
Wei Qian,

Jianlong Su,

Sheng Meng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 29, 2024

Abstract Delayed wound healing is a major complication of diabetes, and associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports microRNA expression in small extracellular vesicles (sEVs), miR‐17‐5p‐engineered sEVs (sEVs 17‐OE ) encapsulated them gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment fabricated. SEVs successfully fabricated 16‐fold increase miR‐17‐5p expression. inhibited senescence promoted proliferation, migration, tube formation high glucose‐induced human umbilical vein endothelial cells (HG‐HUVECs). Additionally, also performs promotive effect dermal fibroblasts (HG‐HDFs). Mechanism analysis showed expressions p21 phosphatase tensin homolog (PTEN), as target genes miR‐17‐5p, downregulated significantly by . Accordingly, downstream pathways PTEN, activated. Next, loaded GelMA to fabricate novel bioactive dressing evaluate their effects healing. Gel‐sEVs effectively accelerated promoting angiogenesis collagen deposition. The mechanism may be local cell proliferation. Therefore, loading hydrogel, offering an option chronic management

Language: Английский

Citations

26
Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles DOI Creative Commons
Victoria Pulido-Escribano,

Bárbara Torrecillas-Baena,

Marta Camacho-Cardeñosa

et al.

World Journal of Stem Cells, Journal Year: 2022, Volume and Issue: 14(7), P. 453 - 472

Published: July 26, 2022

The use of mesenchymal stem-cells (MSC) in cell therapy has received considerable attention because their properties. These properties include high expansion and differentiation vitro, low immunogenicity, modulation biological processes, such as inflammation, angiogenesis hematopoiesis. Curiously, the regenerative effect MSC is partly due to paracrine activity. This prompted numerous studies, investigate therapeutic potential secretome general, specifically extracellular vesicles (EV). latter contain proteins, lipids, nucleic acids, other metabolites, which can cause physiological changes when released into recipient cells. Interestingly, contents EV be modulated by preconditioning under different culture conditions. Among them, exposure hypoxia stands out; these cells respond activating hypoxia-inducible factor (HIF) at O2 concentrations. HIF direct indirect pleiotropic effects, modulating expression hundreds genes involved processes migration, proliferation, differentiation, angiogenesis, metabolism, apoptosis. Expression reflected secreted EV. studies show that MSC-derived conditioned have a higher capacity than those obtained normoxia. In this review, we implications responses relation tissue regeneration. addition, being evaluated very attractive strategy for isolation EV, with clinical medicine applied pathologies.

Language: Английский

Citations

53
Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles DOI Creative Commons

Ziqiang Chu,

Qilin Huang, Kui Ma

et al.

Bioactive Materials, Journal Year: 2023, Volume and Issue: 27, P. 257 - 270

Published: April 14, 2023

Neutrophil extracellular traps (NETs) have been considered a significant unfavorable factor for wound healing in diabetes, but the mechanisms remain unclear. The therapeutic application of small vesicles (sEVs) derived from mesenchymal stem cells (MSCs) has received considerable attention their properties. Hypoxic preconditioning is reported to enhance potential MSC-derived sEVs regenerative medicine. Therefore, aim this study illustrate detailed mechanism NETs impairment diabetic and develop promising NET-targeting treatment based on hypoxic pretreated (Hypo-sEVs). Excessive were found wounds high glucose (HG)-induced neutrophils. Further research showed that concentration impaired function fibroblasts through activating endoplasmic reticulum (ER) stress. Hypo-sEVs efficiently promoted reduced excessive NET formation by transferring miR-17-5p. Bioinformatic analysis RNA interference experiment revealed miR-17-5p obstructed targeting TLR4/ROS/MAPK pathway. Additionally, overexpression decreased overcame NET-induced fibroblasts, similar effects Hypo-sEVs. Overall, we identify previously unrecognized NET-related provide strategy treatment.

Language: Английский

Citations

40
MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration DOI Creative Commons
Hussein H. Genedy, P. Humbert,

Bilel Laoulaou

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 207, P. 115214 - 115214

Published: Feb. 22, 2024

Language: Английский

Citations

13
A new strategy for intervertebral disc regeneration: The synergistic potential of mesenchymal stem cells and their extracellular vesicles with hydrogel scaffolds DOI Open Access
Yan Zhao,

Huaize Dong,

Qiuqiu Xia

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116238 - 116238

Published: Feb. 3, 2024

Intervertebral disc degeneration (IDD) is a disease that severely affects spinal health and prevalent worldwide. Mesenchymal stem cells (MSCs) their derived extracellular vesicles (EVs) have regenerative potential emerged as promising therapeutic tools for treating degenerative discs. However, challenges such the harsh microenvironment of degenerated intervertebral discs EVs' limited stability efficacy hindered clinical application. In recent years, hydrogels attracted much attention in field IDD therapy because they can mimic physiologic provide solution by providing suitable growth environment MSCs EVs. This review introduced biological properties EVs, summarized research on application EVs IDD, current trial studies also explored mechanism action addition, plenty elaborated different classified tissue engineering, synergistic effect promoting regeneration, wide IDD. Finally, problems still faced hydrogel-loaded treatment are summarized, solutions proposed. paper outlines effects combination with aims to theoretical references future related studies.

Language: Английский

Citations

11
Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration DOI Creative Commons
Liang Zhou, Feng Cai,

Zhu Hongyi

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 132 - 152

Published: March 21, 2024

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate IVDD microenvironment reshape extracellular matrix disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology surface chemical modification methods by grafting neutrophil polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto methacrylic gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained long-term release T-NNPs excellent cell-like functions, effectively bound to pro-inflammatory cytokines, improved kinetics TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced in nucleus pulposus cells vitro, downregulated expression metalloproteinase, upregulated collagen-II aggrecan. restored height structure biomechanical function rat model. integration biomimetic nano-drug delivery systems expands application materials provides new treatment strategy IVDD.

Language: Английский

Citations

11
Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy DOI
Linjie Chen, Ke Peng,

He Huang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(32)

Published: April 5, 2024

Abstract The treatment of intervertebral disc degeneration (IVDD) using bone marrow mesenchymal stem cell‐derived exosomes has shown success in alleviating inflammation and restoring the extracellular matrix (ECM), however, challenges persist due to deficiency mechanical support controlled release. Herein, a carbon‐carbon double bond modified keratin (KeMA) is synthesized by 2‐isocyanatoethyl modification for wrapping. This injectable KeMA hydrogel, initiated biocompatible glucose/ glucose oxidase/ horse radish peroxidase enzymatic cascade reaction with acetylacetone N‐vinylpyrrolidone, displayed rapid gelation, resembling nucleus pulposus (NP) elasticity, excellent cytocompatibility. In vitro studies showcased that exosomes‐loaded hydrogel (Exo@KeMA) enhanced exosome release kinetics, suppressed inflammation, fostered (ECM) regeneration, reinstated NP biomechanics. RNA‐seq analysis indicated Exo@KeMA's effects involved PI3K‐Akt signaling regeneration NF‐κB inhibition anti‐inflammation. vivo IVDD rat models demonstrated Exo@KeMA attenuated maintained water content, preserved height, promoted structural regeneration. research introduces an as promising therapy IVDD, facilitating biomechanics restoration, anti‐inflammatory response, ECM

Language: Английский

Citations

8
Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles DOI Creative Commons
Shanfeng Chen,

Yiming Dou,

Yiming Zhang

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 44 - 55

Published: Jan. 1, 2025

Language: Английский

Citations

1
Optimizing therapeutic outcomes: preconditioning strategies for MSC-derived extracellular vesicles DOI Creative Commons
Yuqi Song, Fuxin Liang, Weidong Tian

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) are increasingly recognized for their therapeutic potential in regenerative medicine, driven by capabilities immunomodulation tissue repair. However, MSCs present risks such as immunogenic responses, malignant transformation, the to transmit infectious pathogens due intrinsic proliferative differentiative abilities. In contrast, MSC-EVs, particularly exosomes (MSC-exosomes, 30–150 nm diameter), offer a safer profile. These acellular mitigate associated with immune rejection tumorigenesis inherently incapable of forming ectopic tissues, thereby enhancing clinical safety applicability. This review highlights promise MSC-exosomes especially focusing on modulation miRNA (one bioactive molecules MSC-EVs) profiles through various preconditioning strategies exposure hypoxia, chemotherapeutic agents, inflammatory cytokines, physical stimuli. Such conditioning is shown optimize potential. Key miRNAs including miR-21, miR-146, miR-125a, miR-126, miR-181a noted roles facilitating repair modulating responses. functionalities position valuable tool personalized case exosome-based interventions. Despite this also acknowledged limitations traditional MSC therapies advocates strategic pivot towards modalities enhance outcomes. By discussing recent advances detail identifying remaining pitfalls, aims guide future directions improving efficacy MSC-exosome-based therapeutics. Additionally, variability MSC-EVs presents challenges diverse play regulating gene expression cell behavior. The content can be influenced differences isolation purification methods, which may alter specific miRNAs, contributing effects.

Language: Английский

Citations

1
Extracellular vesicles derived from mesenchymal stem cells confer protection against intervertebral disc degeneration through a microRNA-217-dependent mechanism DOI Creative Commons
Yingjie Hao, Guangduo Zhu, Yu Li

et al.

Osteoarthritis and Cartilage, Journal Year: 2022, Volume and Issue: 30(11), P. 1455 - 1467

Published: Aug. 27, 2022

Language: Английский

Citations

24