Immune exposure: how macrophages interact with the nucleus pulposus

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 14, 2023

Intervertebral disc degeneration (IDD) is a primary contributor to low back pain. Immune cells play an extremely important role in modulating the progression of IDD by interacting with nucleus pulposus (NP) and extracellular matrix (ECM). Encased within annulus fibrosus, healthy NP avascular immune-privileged tissue that does not normally interact macrophages. However, under pathological conditions which neovascularization established damaged disc, establishes extensive crosstalk macrophages, leading different outcomes depending on microenvironmental stimuli. M1 macrophages are class immune predominantly pro-inflammatory promote inflammation ECM degradation NP, creating vicious cycle catabolism drives IDD. In contrast, M2 remodeling repair as primarily involved anti-inflammatory cellular responses. Hence, between type (M1 vs. M2), overall effects could be detrimental or regenerative. Drug surgical treatment can modulate this hence outcomes. This review comprehensively summarizes interaction aiming highlight immunology degeneration.

Language: Английский

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Mesenchymal stromal cell secretome for traumatic brain injury: Focus on immunomodulatory action

Experimental Neurology, Journal Year: 2022, Volume and Issue: 357, P. 114199 - 114199

Published: Aug. 8, 2022

The severity and long-term consequences of brain damage in traumatic injured (TBI) patients urgently calls for better neuroprotective/neuroreparative strategies this devastating disorder. Mesenchymal stromal cells (MSCs) hold great promise have been shown to confer neuroprotection experimental TBI, mainly through paracrine mechanisms via secreted bioactive factors (i.e. secretome), which indicates significant potential a cell-free neuroprotective approach. secretome is composed cytokines, chemokines, growth factors, proteins, lipids, nucleic acids, metabolites, extracellular vesicles; it may offer advantages over MSCs terms delivery, safety, variability therapeutic response injury. Immunomodulation by molecular considered be key mechanism involved their multi-potential effects. Regulated neuroinflammation required healthy remodeling central nervous system during development adulthood. Moreover, immune can also contribute tissue repair neurological recovery following acute However, chronic maladaptive neuroinflammatory exacerbate TBI progressive neurodegeneration impairments. Here, we review the evidence MSC-derived as therapy TBI. Our framework incorporates detailed analysis vitro vivo studies investigating effects on clinically relevant histopathological outcomes. We describe activation after immunomodulatory properties exerted mediators released secretome. then how ageing modifies systemic responses discuss challenges opportunities developing based therapies elderly populations. Finally, aimed at modulating order boost its efficacy will discussed.

Language: Английский

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Immunomodulation in diabetic wounds healing: The intersection of macrophage reprogramming and immunotherapeutic hydrogels

Journal of Tissue Engineering, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Diabetic wound healing presents a significant clinical challenge due to the interplay of systemic metabolic disturbances and local inflammation, which hinder process. Macrophages undergo phenotypic shift from M1 M2 during healing, transition pivotal for effective tissue repair. However, in diabetic wounds, microenvironment disrupts this polarization, perpetuating impeding healing. Reprograming macrophages restore their phenotype offers potential avenue modulating immune promoting This review elucidates mechanisms underlying impaired macrophage polarization toward wounds discusses novel strategies, including epigenetic interventions, promote conversion M2. Hydrogels, with hydrated 3D cross-linked structure, closely resemble physiological extracellular matrix offer advantageous properties such as biocompatibility, tunability, versatility. These characteristics make hydrogels promising candidates developing immunomodulatory materials aimed at addressing wounds. Understanding role immunotherapy, particularly context reprograming, is essential development advanced care solutions. also highlights recent advancements immunotherapeutic step precise treatments

Language: Английский

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Stem Cells: Present Understanding and Prospects for Regenerative Dentistry

Journal of Functional Biomaterials, Journal Year: 2024, Volume and Issue: 15(10), P. 308 - 308

Published: Oct. 15, 2024

Regenerative medicine in dentistry focuses on repairing damaged oral tissues using advanced tools like stem cells, biomaterials, and tissue engineering (TE). Mesenchymal cells (MSCs) from dental sources, such as pulp periodontal ligament, show significant potential for regeneration due to their proliferative differentiative abilities. This systematic review, following PRISMA guidelines, evaluated fifteen studies identified effective strategies improving dental, periodontal, bone through scaffolds, secretomes, bioengineering methods. Key advancements include the use of (DPSCs) ligament (PDLSCs) boost cell viability manage inflammation. Additionally, pharmacological agents matrine surface modifications biomaterials improve adhesion promote osteogenic differentiation. By integrating these approaches, regenerative TE can optimize therapies enhance patient outcomes. review highlights challenges this field, providing a critical assessment current research future directions.

Language: Английский

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Therapeutic potential of total flavonoids of Rhizoma Drynariae: inhibiting adipogenesis and promoting osteogenesis via MAPK/HIF-1α pathway in primary osteoporosis

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 11, 2025

This study seeks to confirm the therapeutic effectiveness of TRFD in inhibiting adipogenesis and promoting osteogenesis primary osteoporosis through MAPK/HIF-1α signaling pathway. C57BL/6J mice underwent ovariectomy (OVX) induce osteoporosis. Mice were administered (Low high doses)estradiol for a duration 12 weeks. Bone microarchitecture evaluated using Micro-CT, while serum biomarkers protein expressions analyzed enzyme-linked immunosorbent assay, Western blotting, immunohistochemistry. Furthermore, BMSC isolated show differentiation, Osteogenic adipogenic induction performed, including ALP activity Oil Red O staining. Bioinformatics analysis RNA sequencing data was conducted identify differentially expressed genes. Total flavonoids Rhizoma Drynariae treatment significantly improved bone reversed histopathological damage OVX mice. It increased levels markers (RUNX2, BMP-2) enhanced MAPK HIF-1α pathways, The results also showed significant dose, TFDR osteogenic differentiation BMSCs suppressing as demonstrated by mineralization, alongside, expression lipid (PPAR-γ, C/EBPα) inhibited. pathway confirmed be crucial mediating these effects. exhibits potential treating These establish an investigation natural option managing Not applicable.

Language: Английский

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IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 20, 2022

Extracellular vesicles (EVs) obtain properties of immunomodulation and tissue repair from their parental mesenchymal stem cells (MSCs), upon delivery may be associated with fewer adverse events. EVs derived adipose-tissue MSCs restored kidney function by attenuating inflammation in a swine model metabolic syndrome (MetS) renal artery stenosis via anti-inflammatory pathways. also ameliorated myocardial injury renovascular hypertension (RVH) secondary to cardiorenal disease, but the mechanisms regulating this effect are unknown. We hypothesize that cytokine interleukin (IL)-10 mediates reparative effects on cardiovascular complications preclinical coexisting MetS RVH. Twenty-three pigs established as Lean controls or RVH models were observed for 16 weeks. At 12 weeks subgroups received an intrarenal 10 11 either wildtype (WT) after IL-10 knockdown (KD) (RVH+WT-EVs RVH+IL-10-KD-EVs, respectively). Cardiac studied in-vivo in-vitro 4 later. showed inflammation, fibrosis, left ventricular diastolic dysfunction. WT-EVs attenuated these impairments, increased capillary density, decreased . In-vitro , co-incubation IL-10-containing activated T-cells proliferation endothelial promoted migration. Contrarily, cardioprotective largely blunted using IL-10-KD-EVs. Thus, pro-angiogenic partly attributed cargo IL-10. Early intervention helpful prevent concurrent

Language: Английский

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Disulfiram Improves Fat Graft Retention by Modulating Macrophage Polarization With Inhibition of NLRP3 Inflammasome-Mediated Pyroptosis

Aesthetic Surgery Journal, Journal Year: 2024, Volume and Issue: 44(7), P. NP501 - NP518

Published: April 2, 2024

Macrophage-mediated inflammatory response in the early post-grafting period restricts fat graft retention. Pyroptosis is a novel type of programmed cell death that extensively participates pathologies.

Language: Английский

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Fascia-derived stem cells enhance fat graft retention by promoting vascularization through the HMOX1-HIF-1α pathway

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

Published: Feb. 25, 2025

Adipose tissue is a widely used autologous soft filler in plastic surgery, particularly for volumetric restoration cases of deficiency. However, effectively controlling the retention rate transplanted fat remains major challenge. Therefore, this study aims to explore strategies enhance graft retention. We isolated fascia-derived stem cells (FDSCs) from human superficial fascia and compared their gene expression profiles with those adipose-derived (ADSCs). Through bioinformatics analysis functional experiments, we identified significant differences angiogenic potential two cell types. Based on sequencing results, further investigated roles hypoxia-inducible factor-1α (HIF-1α) heme oxygenase-1 (HMOX1). This highlights critical FDSCs improving promoting angiogenesis, offering new enhancing survival optimizing regeneration therapies. them RNA was performed analyze profiles, followed by identify potential. Functional experiments were conducted investigate HIF-1α HMOX1 angiogenesis. revealed related angiogenesis FDSCs. The levels HMOX1, HIF-1α, VEGFa significantly higher than ADSCs, positively regulated VEGFa. In vitro demonstrated that promoted more ADSCs. vivo co-transplantation confirmed improved vascularization. can promote vascularization both vivo, improve retention, indicating broad future applications repair regeneration.

Language: Английский

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Postoperative Intermittent Fasting Improves Outcome of Autologous Fat Grafting in Mice

Aesthetic Plastic Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Language: Английский

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Biomechanical Modulation of Dental Pulp Stem Cell (DPSC) Properties for Soft Tissue Engineering

Bioengineering, Journal Year: 2023, Volume and Issue: 10(3), P. 323 - 323

Published: March 3, 2023

Dental pulp regeneration strategies frequently result in hard tissue formation and obliteration. The aim of this study was to investigate whether dental stem cells (DPSCs) can be directed toward soft differentiation by extracellular elasticity. STRO-1-positive human were magnetically enriched cultured on substrates with elasticities 1.5, 15, 28 kPa. morphology DPSCs assessed visually. Proteins relevant mechanobiology ACTB, ITGB1, FAK, p-FAK, TALIN, VINCULIN, PAXILLIN, ERK 1/2, p-ERK 1/2 detected immunofluorescence imaging. Transcription the marker genes BMP2, BMP4, MMP2, MMP3, MMP13, FN1, IGF2 as well cytokines ANGPT1, VEGF, CCL2, TGFB1, IL2, ANG, CSF1 determined using qPCR. A low stiffness, i.e., 1.5 kPa, resulted a tissue-like phenotype gene expression, whereas kPa exhibited signature resembling tissues cytokine expression. Conversely, highest expression observed intermediate elasticity, 15 possibly allowing act "trophic mediators". Our observations highlight impact biophysical cues for DPSC fate enable design scaffold materials clinical that prevent formation.

Language: Английский

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