Implication of Mesenchymal Stem Cells and Their Derivates for Osteochondral Regeneration

Smolinská, Veronika; Debreova, Michaela; Culenova, Martina; Csöbönyeiová, Mária; Švec, Andrey; Danišovič, Ľuboš

doi:10.3390/ijms23052490

Cited by 7 publications

(2 citation statements)

References 114 publications

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“…Therapeutic strategies such as discectomy, microfracture, and autologous chondrocyte transplantation (ACT) alleviate the discomfort caused by disc degeneration and restore mobility, but these therapies do not regenerate the tissue architecture that mimics its native form (1). Therefore, mesenchymal stem cell (MSC) in regenerative medicine has emerged to reduce the chances of the degree of disease invasiveness and donor-side morbidity potentially resulting in superior regenerative potential (19,20). It is the best option with the huge chondrogenic potential and less hypertrophic differentiation.…”

Section: Introductionmentioning

confidence: 99%

Co-regulation of Sox9 and TGFβ1 transcription factors in mesenchymal stem cells regenerated the intervertebral disc degeneration

et al. 2023

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BackgroundIntervertebral disc (IVD) shows aging and degenerative changes earlier than any other body connective tissue. Its repair and regeneration provide a considerable challenge in regenerative medicine due to its high degree of infrastructure and mechanical complexity. Mesenchymal stem cells, due to their tissue resurfacing potential, represent many explanatory pathways to regenerate a tissue breakdown.MethodsThis study was undertaken to evaluate the co-regulation of Sox9 and TGFβ1 in differentiating human umbilical cord mesenchymal stem cells (hUC-MSC) into chondrocytes. The combinatorial impact of Sox9 and TGFβ1 on hUC-MSCs was examined in vitro by gene expression and immunocytochemical staining. In in vivo, an animal model of IVD degeneration was established under a fluoroscopic guided system through needle puncture of the caudal disc. Normal and transfected MSCs were transplanted. Oxidative stress, pain, and inflammatory markers were evaluated by qPCR. Disc height index (DHI), water content, and gag content were analyzed. Histological examinations were performed to evaluate the degree of regeneration.ResultshUC-MSC transfected with Sox9+TGFβ1 showed a noticeable morphological appearance of a chondrocyte, and highly expressed chondrogenic markers (aggrecan, Sox9, TGFβ1, TGFβ2, and type II collagens) after transfection. Histological observation demonstrated that cartilage regeneration, extracellular matrix synthesis, and collagen remodeling were significant upon staining with H&E, Alcian blue, and Masson's trichrome stain on day 14. Additionally, oxidative stress, pain, and inflammatory markers were positively downregulated in the animals transplanted with Sox9 and TGFβ1 transfected MSCs.ConclusionThese findings indicate that the combinatorial effect of Sox9 and TGFβ1 substantially accelerates the chondrogenesis in hUC-MSCs. Cartilage regeneration and matrix synthesis were significantly enhanced. Therefore, a synergistic effect of Sox9 and TGFβ1 could be an immense therapeutic combination in the tissue engineering of cartilaginous joint bio-prostheses and a novel candidate for cartilage stabilization.

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Section: Introductionmentioning

confidence: 99%

Co-regulation of Sox9 and TGFβ1 transcription factors in mesenchymal stem cells regenerated the intervertebral disc degeneration

et al. 2023

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“…It has been well demonstrated that there is a complex interplay among cells [T cells, B cells, plasma cells, mast cells, stromal cells, fibroblast-like synoviocytes (FLS), and macrophages], and soluble immune mediators are the major players in joint inflammation [ 11 ]. FLS, the main constituent cells in the synovium, maintain homeostasis in synovial tissue extracellular matrix and SF.…”

Section: Introductionmentioning

confidence: 99%

High levels of TDO2 in relation to pro-inflammatory cytokines in synovium and synovial fluid of patients with osteoarthritis

Rong

Zhang

et al. 2022

BMC Musculoskelet Disord

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Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme that catabolizes tryptophan to kynurenine. Numerous studies have suggested that TDO2 is involved in inflammation-related diseases. However, its role in osteoarthritis (OA) has not yet been investigated. The aim of the present study was to explore the levels of TDO2 in the synovium and synovial fluid (SF) of patients with OA and its correlation with clinical manifestations and levels of pro-inflammatory cytokines. Methods Synovium and SF samples were collected from patients with OA and patients with joint trauma (controls) during surgery. An enzyme-linked immunosorbent assay (ELISA) was used to measure TDO2, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Diagnostic performance of TDO2 in the synovium to discriminate between controls and OA patients was assessed using receiver operating characteristic (ROC) curve analysis. Correlations between TDO2 levels, OA clinical features, and pro-inflammatory cytokines were evaluated using Pearson correlation analysis. Effects of IL-1β or TNF-α stimulation on TDO2 expression in OA-fibroblast-like synoviocytes (OA-FLS) were also examined. Results The levels of TDO2, IL-1β, and TNF-α in the synovium of patients with OA were found to be significantly higher than those in controls. ROC curve analysis revealed an area under the curve (AUC) of 0.800 with 64.3% sensitivity and 85.0% specificity of TOD2 in the synovium, which enabled discriminating patients with OA from controls. Moreover, protein expression of TDO2 was upregulated to a greater extent in OA-FLS than in normal synovial fibroblasts (NSF). Furthermore, the levels of TDO2 showed significantly positive correlation with IL-1β and TNF-α levels in the synovium and SF. TDO2 levels in the synovium were also positively correlated with the Kellgren-Lawrence score. Additionally, TDO2 protein expression was significantly increased in IL-1β‒ or TNF-α‒stimulated OA-FLS than in control FLS. Conclusion These data indicate that highTDO2 levels in the synovium can be correlated with pro-inflammatory cytokines and severity of OA.

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Collagen-based bioinks for regenerative medicine: Fabrication, application and prospective

Ruan¹,

Niu²

2023

Medicine in Novel Technology and Devices

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Implication of Mesenchymal Stem Cells and Their Derivates for Osteochondral Regeneration

Cited by 7 publications

References 114 publications

Co-regulation of Sox9 and TGFβ1 transcription factors in mesenchymal stem cells regenerated the intervertebral disc degeneration

Co-regulation of Sox9 and TGFβ1 transcription factors in mesenchymal stem cells regenerated the intervertebral disc degeneration

High levels of TDO2 in relation to pro-inflammatory cytokines in synovium and synovial fluid of patients with osteoarthritis

Collagen-based bioinks for regenerative medicine: Fabrication, application and prospective

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