Acute or chronic depletion of macrophages in the dorsal root ganglia induces neuropathic pain after unilateral cervical spinal cord injury DOI Open Access

Soha J. Chhaya,

Jonathan Houston Richards,

Grace A. Giddings

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 13, 2023

Abstract The inflammatory response at the spinal cord injury (SCI) epicenter and heightened macrophage presence in dorsal root ganglia (DRG) has been well characterized after SCI correlates with neuropathic pain. CCL2, a chemokine that acts as chemoattractant neuromodulator, is implicated pain development, however, role of CCL2-CCR2 axis development not explored. Here, we examined signaling recruitment to DRG prolonged macrophages on persistence SCI. Adult female Sprague-Dawley rats received moderate, unilateral C5 contusion. Sandwich ELISA revealed CCL2 upregulated ipsilesional C7 C8 DRGs first 24 hours post (hpi) returns naïve levels by 72 hpi. To prevent monocyte-derived DRG, additional vehicle or INCB3344, CCR2 antagonist, intravenously time 48 INCB3344 administration induced transient forepaw allodynia 7dpi nearly all (88%) compared only 33% controls resolves partially 28 dpi, measured von Frey mechanical conflict avoidance paradigms. As expected, qPCR analyses whole reduced markers cytokines 7 dpi treated rats. By there were no significant differences between vehicle-treated groups, indicating SCI-induced delayed treatment. Moreover, gene expression polarity suggest pro-inflammatory environment 28dpi. ablation via liposomal clodronate 21dpi did ameliorate hypersensitive behavior, though their reduce paw withdrawal thresholds previously demonstrate behavior. Collectively, these data driving pro-reparative phenotype may be viable effective analgesic strategy modulating both immune experience

Language: Английский

The Anti-Inflammatory Effects of Formononetin, an Active Constituent of Pueraria montana Var. Lobata, via Modulation of Macrophage Autophagy and Polarization DOI Creative Commons

Linyi Xu,

Shuo Zhou, Jing Li

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(1), P. 196 - 196

Published: Jan. 6, 2025

Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa Predeep (P. lobata) is a medicinal herb widely used in the food and pharmaceutical industries, studies have shown that P. possesses significant anti-inflammatory pharmacological activities. In this paper, total of 16 compounds were isolated identified from lobata, among which 1–3, 7, 14, for first time. The results an vitro activity screening assay showed 1, 4, 6, 8, 15 able to significantly reduce levels pro-inflammatory cytokines IL-6 IL-1β LPS-induced RAW264.7 macrophages, with most obvious effect produced by compound 6 (formononetin), while formononetin was number macrophages at site inflammation transgenic zebrafish. addition, network analysis revealed closely related autophagy polarization targets such as TNF, EGFR, PTGS2, ESR1. validation experiments could enhance expression LCII/LCI P62 protein, CD86, CD206, further indicated regulating macrophage processes.

Language: Английский

Citations

1

Isolation, identification, and challenges of extracellular vesicles: emerging players in clinical applications DOI
Xiaoxiao Ma, Linbo Peng, Xiaohui Zhu

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 10, 2024

Language: Английский

Citations

7

Hydrogel-encapsulated extracellular vesicles for the regeneration of spinal cord injury DOI Creative Commons
Yasaman Nazerian, Amirhossein Nazerian,

Fereshteh Mohamadi-Jahani

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Dec. 14, 2023

Spinal cord injury (SCI) is a critical neurological condition that may impair motor, sensory, and autonomous functions. At the cellular level, inflammation, impairment of axonal regeneration, neuronal death are responsible for SCI-related complications. Regarding high mortality morbidity rates associated with SCI, there need effective treatment. Despite advances in SCI repair, an optimal treatment complete recovery after has not been found so far. Therefore, strategy needed to promote regeneration repair SCI. In recent years, regenerative treatments have become potential option achieving improved functional by promoting growth new neurons, protecting surviving preventing additional damage spinal cord. Transplantation cells cells-derived extracellular vesicles (EVs) can be recovery. However, some limitations challenges related cell-based strategies. Ethical concerns limited efficacy due low survival rate, immune rejection, tumor formation therapies. Using EVs helpful overcome these limitations. It should considered short half-life, poor accumulation, rapid clearance, difficulty targeting specific tissues EVs-based Hydrogel-encapsulated exosomes enhancing through maintaining their bioactivity, from facilitating sustained release at target site. These hydrogel-encapsulated neuroregeneration improving recovery, reducing This review aims provide overview current research status, challenges, future clinical opportunities

Language: Английский

Citations

10

Exploring the therapeutic potential of small extracellular vesicles derived from induced pluripotent stem cell in periodontal regeneration DOI
Tingting Xu, Yi Peng,

Yanan Xu

et al.

Journal of Oral Biosciences, Journal Year: 2025, Volume and Issue: unknown, P. 100621 - 100621

Published: Jan. 1, 2025

Language: Английский

Citations

0

Effects of Hydrogels on Mesenchymal Stem/Stromal Cells Paracrine Activity and Extracellular Vesicles Production DOI Creative Commons

Oscar Fabian Garcia‐Aponte,

Simon Kahlenberg,

Dimitrios Kouroupis

et al.

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(3)

Published: March 1, 2025

ABSTRACT Mesenchymal stem/stromal cells (MSCs) are a valuable source of paracrine factors, as they have remarkable secretory capacity, and there is sizeable knowledge base to develop industrial clinical production protocols. Promising cell‐free approaches for tissue regeneration immunomodulation driving research towards secretome applications, among which extracellular vesicles (EVs) steadily gaining attention. However, the manufacturing application EVs limited by insufficient yields, gaps, low standardization. Facing these limitations, hydrogels represent versatile three‐dimensional (3D) culture platform that can incorporate matrix (ECM) components mimic natural stem cell environment in vitro; via niche‐mimicking properties, regulate MSCs’ morphology, adhesion, proliferation, differentiation secretion capacities. impact hydrogel's architectural, biochemical biomechanical properties on remains poorly understood, field still its infancy interdependency parameters compromises comparability studies. Therefore, this review summarizes discusses reported effects hydrogel encapsulation MSC‐EVs. Considering cell‐material interactions overall activity MSCs, we identify persistent challenges from standardization process control, outline future paths research, such synergic use bioreactors enhance MSC‐EV generation.

Language: Английский

Citations

0

Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy DOI Creative Commons

Michelle Combe,

Kathy Sharon Isaac,

Jordan R. Plews

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 4, 2025

Extracellular vesicles (EVs) contain a variety of proteins with anti-inflammatory and immunomodulatory properties that offer promising benefits in skin therapy applications. An influx EV proteomic studies recent years has created the opportunity for detailed comparison heterogeneity between context therapeutic Although several process conditions are known to cause variability EVs, little been done quantify impact these factors on nature protein cargo. This review aims both compile publicly available proteomics data quantitatively estimate. cargo-particularly Of roughly 400 articles, 52 relevant were identified within last 15 years. Across studies, 40% 13,000 observed only single study. EVs general found be highly variable, mixed effects models able account 25-60% variance when considering such as source, medium, isolation method, LC-MS ionization, search algorithm. Overall, MSC-derived contained greater fraction pathways associated wound healing (immune system, hemostasis, extracellular matrix organization, cellular response stress) well most number unique compared all other analysed EVs. tool therapeutics, overall cargo underscores need standardized methodologies fully elucidate

Language: Английский

Citations

0

Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation DOI Creative Commons
Hongjie Xu, Bin Wang, Ang Li

et al.

Aging and Disease, Journal Year: 2023, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2023

Emerging from several decades of extensive research, key genetic elements and biochemical mechanisms implicated in neuroinflammation have been delineated, contributing substantially to our understanding neurodegenerative diseases (NDDs). In this minireview, we discuss data predominantly the past three years, highlighting pivotal roles two principal cell types neuroinflammation. The review also underscores extended process peripheral inflammation that predates symptomatic onset, critical influence neuroinflammation, their dynamic interplay pathogenesis NDDs. Confronting these complex challenges, introduce compelling evidence supporting use mesenchymal stem cell-based cell-free therapy. This therapeutic strategy includes regulation microglia astrocytes, modulation nerve inflammation, targeted anti-inflammatory interventions specifically designed for NDDs, while discussing engineering safety considerations. innovative approach intricately modulates immune system across nervous systems, with an emphasis on achieving superior penetration delivery. insights offered by significant implications better management

Language: Английский

Citations

6

Emerging Role and Mechanism of Mesenchymal Stem Cells-Derived Extracellular Vesicles in Rheumatic Disease DOI Creative Commons
Zhangxue Wang, Chunjuan Yang, Shushan Yan

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 6827 - 6846

Published: Sept. 1, 2024

Mesenchymal stem cells (MSCs) are pluripotent derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) the primary mechanism for regulation of MSCs. They deliver proteins, nucleic acids, lipids, other active compounds to various tissues organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs MSC-derived EVs (MSC-EVs) due their immunomodulatory capabilities, according mounting data. Since MSC-EVs have low immunogenicity, high stability, similar effects as themselves, advantageous over cell therapy potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, sclerosis, Sjogren's syndrome, diseases. This review integrates recent advances characteristics, functions, molecular mechanisms rheumatic provides a new understanding pathogenesis MSC-EV-based treatment strategies.

Language: Английский

Citations

2

The role of microglia in neurological diseases with involvement of extracellular vesicles DOI Creative Commons
Haotian Xie, Feifeng Wu,

Jueyi Mao

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 202, P. 106700 - 106700

Published: Oct. 12, 2024

As a subset of mononuclear phagocytes in the central nervous system, microglia play crucial role immune defense and homeostasis maintenance. Microglia can regulate their states response to specific signals health pathology. Microglia-mediated neuroinflammation is pathological hallmark neurodegenerative diseases, neurological damage tumors, underscoring its key immunoregulatory these conditions. Intriguingly, substantial body research has indicated that extracellular vesicles mediate intercellular communication by transporting cargoes from parental cells, property also reflected microenvironmental signaling networks involving microglia. Based on microglial characteristics, we briefly outline biological features focus summarizing integrative played maintenance system progression different diseases. Extracellular may engage process as medium communication. Here, aim provide new insights for further exploration disease pathogenesis, which theoretical foundations cell-free therapies.

Language: Английский

Citations

2

Immune-regulatory properties of endovascular extravillous trophoblast cells in human placenta DOI
Yeling Ma, Xin Yu,

Sheng‐Long Ye

et al.

Placenta, Journal Year: 2023, Volume and Issue: 145, P. 107 - 116

Published: Dec. 12, 2023

Language: Английский

Citations

5