High-yield extracellular vesicle production from HEK293T cells encapsulated in 3D auxetic scaffolds with cyclic mechanical stimulation for effective drug carrier systems DOI

Yi-Wen Chen,

Yen-Hong Lin,

Chia-Che Ho

et al.

Biofabrication, Journal Year: 2024, Volume and Issue: 16(4), P. 045035 - 045035

Published: Aug. 22, 2024

Abstract Extracellular vesicles (EVs) show promise in drug loading and delivery for medical applications. However, the lack of scalable manufacturing processes hinders generation clinically suitable quantities, thereby impeding translation EV-based therapies. Current EV production relies heavily on non-physiological two-dimensional (2D) cell culture or bioreactors, requiring significant resources. Additionally, EV-derived ribonucleic acid cargo three-dimensional (3D) 2D environments remains largely unknown. In this study, we optimized biofabrication 3D auxetic scaffolds encapsulated with human embryonic kidney 293 T (HEK293 T) cells, focusing enhancing mechanical properties to significantly boost through tensile stimulation bioreactors. The proposed platform increased yields approximately 115-fold compared conventional culture, possessing that inhibit tumor progression. Further mechanistic examinations revealed effect was mediated by mechanosensitivity YAP/TAZ. EVs derived from tensile-stimulated HEK293 cells demonstrated superior capability doxorubicin their counterparts cancer therapy. Our results underscore potential strategy scaling up optimizing functional performance clinical translation.

Language: Английский

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

Qixuan Yu

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: June 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.

Language: Английский

Citations

61

Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade DOI Creative Commons
Saeid Moghassemi, Arezoo Dadashzadeh, Maria João Sousa

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 36, P. 126 - 156

Published: March 2, 2024

Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. nanovesicles possess several desirable properties, making them ideal for regenerative medicine nanomedicine applications. properties include exceptional stability, biocompatibility, wide biodistribution, minimal immunogenicity. However, the practical utilization particularly clinical settings at large scale, is hindered expensive procedures required their isolation, limited circulation lifetime, suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated remarkable ability accommodate various cargoes found extensive applications biomedical sciences. To overcome limitations broaden potential applications, researchers should strive deepen understanding current loading, characterization techniques. Additionally, acquiring fundamental knowledge about origins employing state-of-the-art methodologies expand research scope. This review provides comprehensive overview exosome-based strategies diverse domains, encompassing cancer therapy, immunotherapy, biomarker Furthermore, we emphasize immense exosomes medicine.

Language: Английский

Citations

33

Advancements in tissue engineering for articular cartilage regeneration DOI Creative Commons
Maohua Chen, Zhiyuan Jiang,

Xiuyuan Zou

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e25400 - e25400

Published: Feb. 1, 2024

Articular cartilage injury is a prevalent clinical condition resulting from trauma, tumors, infection, osteoarthritis, and other factors. The intrinsic lack of blood vessels, nerves, lymphatic vessels within tissue severely limits its self-regenerative capacity after injury. Current treatment options, such as conservative drug therapy joint replacement, have inherent limitations. Achieving perfect regeneration repair articular remains an ongoing challenge in the field regenerative medicine. Tissue engineering has emerged key focus research, aiming to utilize cultured expanded cells combined with suitable scaffold materials create viable, functional tissues. This review article encompasses latest advancements seed cells, scaffolds, cytokines. Additionally, role stimulatory factors including cytokines growth factors, genetic techniques, biophysical stimulation, bioreactor systems, well scaffolding natural synthetic nanostructured scaffolds tissues are discussed. Finally, we also outline signaling pathways involved regeneration. Our provides valuable insights for scholars address complex problem repair.

Language: Английский

Citations

25

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity DOI Creative Commons

Zhengang Ding,

Zineng Yan,

Xun Yuan

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 23, 2024

Due to its unique structure, articular cartilage has limited abilities undergo self-repair after injury. Additionally, the repair of injury always been a difficult problem in field sports medicine. Previous studies have shown that therapeutic use mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) great potential for promoting repair. Recent demonstrated most transplanted apoptosis vivo, apoptotic EVs (ApoEVs) are subsequently generated play crucial roles tissue MSCs known exist under low-oxygen conditions physiological environment, these hypoxic can alter functional secretory properties as well secretomes. This study aimed investigate whether ApoEVs isolated from adipose-derived cultured (hypoxic [H-ApoEVs]) exert greater effects on than those normoxic conditions. Through vitro cell proliferation migration experiments, we H-ApoEVs exerted enhanced proliferation, migration, bone marrow derived macrophages (BMDMs) M

Language: Английский

Citations

17

Differentiation of stem cells into chondrocytes and their potential clinical application in cartilage regeneration DOI
Julia Cieśla, Marcin Tomsia

Histochemistry and Cell Biology, Journal Year: 2025, Volume and Issue: 163(1)

Published: Jan. 25, 2025

Language: Английский

Citations

1

Mesenchymal stem cell–derived extracellular vesicles in joint diseases: Therapeutic effects and underlying mechanisms DOI Creative Commons

Jinhui Wu,

Jiangyi Wu, Zheng Liu

et al.

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 48, P. 53 - 69

Published: July 27, 2024

Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint have several limitations, such as unsatisfatory efficacy side effects, necessitating exploration more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) demonstrated high efficacyin tissue repair regeneration, with low immunogenicity tumorigenicity. Recent studies reported that EVs-based therapy has considerable effects against diseases, including osteoarthritis, tendon ligament injuries, femoral head osteonecrosis, rheumatoid arthritis. Herein, we review potential various types MSC-EVs in aforementioned summarise mechanisms underlying specific biological MSC-EVs, discuss future prospects basic research on MSC-EV-based modalities their clinical translation. In general, this provides an in-depth understanding well mechanisms, which may be beneficial to translation treatment. The translational article: cell-free can effectively promote regeneration repair. When used treat desirable preclinical research. This supplement further treatment its

Language: Английский

Citations

7

The exosomal secretomes of mesenchymal stem cells extracted via 3D-printed lithium-doped calcium silicate scaffolds promote osteochondral regeneration DOI Creative Commons
Tsung-Li Lin, Yen-Hong Lin, Alvin Kai-Xing Lee

et al.

Materials Today Bio, Journal Year: 2023, Volume and Issue: 22, P. 100728 - 100728

Published: July 19, 2023

The development of surface modification techniques has brought about a major paradigm shift in the clinical applications bone tissue regeneration. Biofabrication strategies enable creation scaffolds with specific microstructural environments and biological components. Lithium (Li) been reported to exhibit anti-inflammatory, osteogenic, chondrogenic properties by promoting several intracellular signaling pathways. Currently, research focuses on fabricating simultaneous dual bioactivities enhance osteochondral In this study, we modified calcium silicate (CS) Li using simple immersion technique evaluated their capabilities for results showed that ions could be easily coated onto surfaces CS without affecting itself. Furthermore, modifications did not affect printing CS, porous fabricated via extrusion. Moreover, presence improved roughness hydrophilicity, thus leading enhanced secretion osteochondral-related regeneration factors, such as alkaline phosphatase (ALP), sialoprotein (BSP), collagen II (Col II) proteins. Subsequent vivo studies, including histological micro-CT analyses, confirmed Li-modified promoted transcriptome analysis suggested osteochondrogenic our were influenced paracrine exosomes. We hope study will inspire further

Language: Английский

Citations

15

Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis DOI Creative Commons
Zehao Zhang, Sheng Zhao,

Zhaofeng Sun

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Sept. 28, 2023

Abstract Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is major source of pain and disability worldwide. Despite current treatments, overall treatment outcome unsatisfactory. Thus, patients severe OA often require replacement surgery. In recent years, mesenchymal stem cells (MSCs) have emerged promising therapeutic option for preclinical clinical palliation OA. MSC-derived exosomes (MSC-Exos) carrying bioactive molecules parental cells, including non-coding RNAs (ncRNAs) proteins, demonstrated significant impact on modulation various physiological behaviors in cavity, making them candidates cell-free therapy This review provides comprehensive overview biosynthesis composition MSC-Exos their mechanisms action We also discussed potential tool modulating intercellular communication Additionally, we explored bioengineering approaches to enhance MSC-Exos’ potential, which may help overcome challenges achieve clinically meaningful therapies.

Language: Английский

Citations

15

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells DOI Creative Commons
Wenya Chen, Peipei Wu, Can Jin

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 1, 2024

Abstract Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component stem cell potency, overcome drawbacks cell-free therapeutic agent play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture SCs low yield face challenges large-scale production, which hinders clinical translation EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate vivo environment, can not only expand large quantities, but also improve activity EVs, changing content improving effects. In this review, we briefly describe advantages EV-related applications, provide overview 3D finally focus on specific future perspectives different SCs. Graphical

Language: Английский

Citations

6

Direct and cell-mediated EV-ECM interplay DOI
Olga Smirnova, Yuri M. Efremov, Timofey O. Klyucherev

et al.

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 186, P. 63 - 84

Published: July 21, 2024

Language: Английский

Citations

5