The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells

Cao, Lei; Yan, Xinxin; Liu, Guangwang; Yu, Degang; Li, Huiwu; Fan, Qiming; Gan, Yaokai; Tang, Tingting; Dai, Kerong

doi:10.1016/j.biomaterials.2011.02.014

Cited by 107 publications

(121 citation statements)

References 45 publications

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“…Cartilage tissue has a very limited capacity for spontaneous healing or repair after articular cartilage defects (micro-or macrotrauma), presenting an increasing problem for humans and animals, which necessitates the development of novel and improved therapeutic strategies (49). Moreover, cartilage tissue engineering from primary chondrocytes is to date unsatisfactory, mainly due to the fact that the long culturing period leads to dedifferentiation of chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Sirtuin-1 (SIRT1) Is Required for Promoting Chondrogenic Differentiation of Mesenchymal Stem Cells

Buhrmann

Busch

Shayan

et al. 2014

Journal of Biological Chemistry

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Background: Molecular signaling during chondrogenic differentiation of mesenchymal stem cells (MSC) is poorly understood. Results: Knockdown of sirtuin-1 (SIRT1) in MSC induced inhibition of chondrogenesis, Sox9 expression, up-regulation of nuclear factor-B (NF-B) phosphorylation and acetylation, and NF-B-dependent pro-inflammatory enzymes. Conclusion: SIRT1 supports chondrogenic differentiation of MSCs by Sox9 activation and NF-B deacetylation. Significance: These findings may be essential for improving cartilage tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

Sirtuin-1 (SIRT1) Is Required for Promoting Chondrogenic Differentiation of Mesenchymal Stem Cells

Buhrmann

Busch

Shayan

et al. 2014

Journal of Biological Chemistry

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“…SOX-9 is expressed in all chondroprogenitor cells, predominantly in mesenchymal condensations and cartilage. Cao et al also found that the repair of cartilage defects can be enhanced by SOX-9 transduction [16]. They reported that the articular cartilage defects treated with MSC overexpressing SOX-9 showed the significantly better integration of the repair tissue at the interface with the surrounding normal articular cartilage when compared to the other groups.…”

Section: Resultsmentioning

confidence: 98%

Immunohistochemistry Evaluation of TGF-β1, SOX-9, Type II Collagen and Aggrecan in Cartilage Lesions Treated with Conditioned Medium of Umbilical Cord Mesencyhmal Stem Cells in Wistar Mice (Rattus novergicus)

Soetjahjo

Hidayat

Sujuti

et al. 2018

J.Trop.Life.Science

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Currently, umbilical cord mesenchymal stem cells have the potential to be used as treatment options for any cartilage lesion. This research aimed to evaluate the effects of conditioned medium from umbilical cord mesenchymal stem cells (UC-MSC) on damaged cartilage through the expression of proteins TGF-β1, SOX-9, type II collagen and aggrecan, which are known to be related to chondrogenesis. UC-MSC were isolated from 19-days-pregnant Wistar mice and were cultured using the standard procedure to obtain 80% confluence. Subsequently, the culture was confirmed through a microscopic examination that was driven to be an embryoid body to obtain a pre-condition medium. This research utilized 3-month-old male Wistar mice and was categorized into 6 groups (3 control and 3 treatment groups). Each animal had surgery performed to create a femur condyle cartilage defect. The treatment groups were administered a dose of stem cells at 1 mL/kg. Next, immunohistochemical (IHC) staining was performed to examine the expression of TGF-β1, SOX-9, type II collagen and aggrecan in the 2 nd , 3 rd , and 4 th month of evaluation. The results were analyzed statistically using ANOVA test. For each of the treatment groups, there was increased expression (p < 0.05) in all proteins TGF-β1, SOX-9, type II collagen and aggrecan when compared with control groups at the 2 nd , 3 rd , and 4 th month of evaluation. Pre-conditioned medium from UC-MSC potentially increases the expression of TGF-β1, SOX-9, type II collagen and aggrecan in the damaged cartilage of Wistar mice.

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“…SOXs regulate chondrocyte differentiation, improve ECM production and reduce the levels of hypertrophy and osteogenic/ adipogenic markers. ZNF145 regulates the differentiation of 3-lineages of MSCs, as observed in in vitro studies [54,59,65,77], while in vivo it increases osteochondral and full-thickness defects healing [54,59,75]. The co-infection of SOX9 and TGF-β potentiates chondrogenesis of MSCs in vitro, in comparison to their separate use [64].…”

Section: Transcription Factorsmentioning

confidence: 90%

“…Genes, in encapsuled viral [24] vector, can be injected directly in vivo [50,51] or through decalcified cortical bone matrix (DCBM) as scaffold that contains the viral particles [52]. Indian hedgehog homolog (iHH) and SOXs genes employ adenovirus for transport into MSCs both in vitro [53,54] and in vivo [55,56]. Antiinflammatory cytokines are introduced into Fibroblasts (FBs) or directly injected in vivo [56,57] (Table 1).…”

Section: Viral Vectormentioning

confidence: 99%

“…The combination of gene therapy and scaffolds seems to greatly enhance both the efficiency and duration of transfected genes, leading to systems able to promote bone, cartilage, and osteochondral regeneration [22,23,26]. Scaffolds can be natural such as DBM, gelatine, alginate, fibrinogen and collagen based [16-18, 21, 27, 46, 52, 62, 71, 73, 84], or synthetic such as polyglycolic acid (PGA), polylactic acid (PLA) and poly(lactic-co-glycolide) (PLGA) [14,42,54,[82][83][84] (Table 1). Besides favouring cell engineering within the scaffold, their design can be used as guide for the correct integration and directional localization of cells in the defect.…”

Section: Use Of Scaffold In Gene Therapy Proceduresmentioning

confidence: 99%

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Gene therapy for chondral and osteochondral regeneration: is the future now?

Bellavia

Veronesi

Carina

et al. 2017

Cell. Mol. Life Sci.

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Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies. Genes delivered encoded mainly for growth factors, followed by transcription factors, anti-inflammatory cytokines and, less frequently, by cell signalling proteins, matrix proteins and receptors. Direct injection of the expression vector was used less than indirect injection of cells, with or without scaffolds, transduced with genes of interest and then implanted into the lesion site. Clinical trials (phases I, II or III) on safety, biological activity, efficacy, toxicity or bio-distribution employed adenovirus viral vectors to deliver growth factors or anti-inflammatory cytokines, for the treatment of osteoarthritis or degenerative arthritis, and tumour necrosis factor receptor or interferon for the treatment of inflammatory arthritis

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The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells

Cited by 107 publications

References 45 publications

Sirtuin-1 (SIRT1) Is Required for Promoting Chondrogenic Differentiation of Mesenchymal Stem Cells

Sirtuin-1 (SIRT1) Is Required for Promoting Chondrogenic Differentiation of Mesenchymal Stem Cells

Immunohistochemistry Evaluation of TGF-β1, SOX-9, Type II Collagen and Aggrecan in Cartilage Lesions Treated with Conditioned Medium of Umbilical Cord Mesencyhmal Stem Cells in Wistar Mice (Rattus novergicus)

Gene therapy for chondral and osteochondral regeneration: is the future now?

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