Gene Modification of Mesenchymal Stem Cells and Articular Chondrocytes to Enhance Chondrogenesis

Gurusinghe, Saliya; Strappe, Pádraig

doi:10.1155/2014/369528

Cited by 19 publications

(15 citation statements)

References 82 publications

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“…More recently, a novel strategy of using genetically modified MSCs in OA therapy has been developed [26]. By exploiting its self‐renewal property, MSCs can be used as delivery vehicles for exogenous expression of specific genes that can contribute to alleviation of OA symptoms [27].…”

Section: Introductionmentioning

confidence: 99%

Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development

Xia

Zhu

et al. 2015

Stem Cells Translational Medicine

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Osteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α (TNFα) has been identified as a crucial effector modulating OA pathogenesis. This study aimed to investigate the therapeutic effects of Atsttrin, a novel TNFα blocker, on OA treatment. We developed genetically modified mesenchymal stem cells (MSCs) that expressed recombinant Atsttrin (named as MSC-Atsttrin). Expression levels of ADAMTS-5, MMP13, and iNOS of human chondrocytes were analyzed when cocultured with MSC-GFP/Atsttrin. OA animal models were induced by anterior cruciate ligament transection, and MSC-GFP/Atsttrin were injected into the articular cavity 1 week postsurgery. The results showed that MSC-Atsttrin significantly suppressed TNFα-driven up-regulation of matrix proteases and inflammatory factors. Intra-articular injection of MSC-Atsttrin prevented the progression of degenerative changes in the surgically induced OA mouse model. Additionally, levels of detrimental matrix hydrolases were significantly diminished. Compared with nontreated OA samples at 8 weeks postsurgery, the percentages of MMP13- and ADAMTS-5-positive cells were significantly reduced from 91.33% ± 9.87% to 24.33% ± 5.7% (p < .001) and from 91.33% ± 7.1% to 16.67% ± 3.1% (p < .001), respectively. Our results thus indicated that suppression of TNFα activity is an effective strategy for OA treatment and that intra-articular injection of MSCs-Atsttrin could be a promising therapeutic modality.

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Section: Introductionmentioning

confidence: 99%

Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development

Xia

Zhu

et al. 2015

Stem Cells Translational Medicine

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“…Of these compounds, miR148b has been shown to induce de novo osteogenesis in bone marrow-derived MSC and ASC and has been demonstrated to enhance progenitor osteogenesis and bone repair both in vitro and in vivo [79,[81][82][83] . Several miRNAs such as miR-146a, miR-9, miR-29a and miR-140 play a role in the regulation of chondrogenesis [84][85][86][87][88][89] . In addition, different drug delivery systems can be incorporated into "bioinks" and be deposited in regions that require controlled release of cell-signaling molecules [90] .…”

Section: Towards Mimicking the Heterogeneity And Anisotropymentioning

confidence: 99%

Bioprinting of osteochondral tissues: A perspective on current gaps and future trends

Datta

Dhawan

et al. 2024

IJB

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Abstract:Osteochondral tissue regeneration has remained a critical challenge in orthopaedic surgery, especially due to complications of arthritic degeneration arising out of mechanical dislocations of joints. The common gold standard of autografting has several limitations in presenting tissue engineering strategies to solve the unmet clinical need. However, due to the complexity of joint anatomy, and tissue heterogeneity at the interface, the conventional tissue engineering strategies have certain limitations. The advent of bioprinting has now provided new opportunities for osteochondral tissue engineering. Bioprinting can uniquely mimic the heterogeneous cellular composition and anisotropic extra-cellular matrix (ECM) organization, while allowing for targeted gene delivery to achieve heterotypic differentiation. In this perspective, we discuss the current advances made towards bioprinting of composite osteochondral tissues and present an account of challenges-in terms of tissue integration, long-term survival, and mechanical strength at the time of implantation-required to be addressed for effective clinical translation of bioprinted tissues. Finally, we highlight some of the future trends related to osteochondral bioprinting with the hope of in-clinical translation. Keywords: bioprinting; osteochondral injuries; zonal anisotropy; bioink; tissue engineering

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“…Additionally, the genetic manipulation of microRNAs in human MSCs has been shown to promote chondrogenesis . Strategies using genetically manipulated cells offer significant potential, however, a future challenge will be to ensure an appropriate safety profile while still preserving clinical efficacy …”

Section: Stimulatory Signals For Chondrogenesismentioning

confidence: 99%

“…The genetic modification of MSCs using viral or non-viral vectors has also emerged as a potential technique for chondrogenic enhancement. [63] MSCs transfected with BMP-2 and SOX-9 have been reported to promote chondrogenesis in murine models. [64,65] Additionally, the genetic manipulation of microRNAs in human MSCs has been shown to promote chondrogenesis.…”

Section: Biomaterials For Cartilage Regenerative Medicine Strategiesmentioning

confidence: 99%

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Mesenchymal Stem Cells: Potential Role in the Treatment of Osteochondral Lesions of the Ankle

Tribe

McEwan

Taylor

et al. 2017

Biotechnology Journal

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Given articular cartilage has a limited repair potential, untreated osteochondral lesions of the ankle can lead to debilitating symptoms and joint deterioration necessitating joint replacement. While a wide range of reparative and restorative surgical techniques have been developed to treat osteochondral lesions of the ankle, there is no consensus in the literature regarding which is the ideal treatment. Tissue engineering strategies, encompassing stem cells, somatic cells, biomaterials, and stimulatory signals (biological and mechanical), have a potentially valuable role in the treatment of osteochondral lesions. Mesenchymal stem cells (MSCs) are an attractive resource for regenerative medicine approaches, given their ability to self‐renew and differentiate into multiple stromal cell types, including chondrocytes. Although MSCs have demonstrated significant promise in in vitro and in vivo preclinical studies, their success in treating osteochondral lesions of the ankle is inconsistent, necessitating further clinical trials to validate their application. This review highlights the role of MSCs in cartilage regeneration and how the application of biomaterials and stimulatory signals can enhance chondrogenesis. The current treatments for osteochondral lesions of the ankle using regenerative medicine strategies are reviewed to provide a clinical context. The challenges for cartilage regeneration, along with potential solutions and safety concerns are also discussed.

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Gene Modification of Mesenchymal Stem Cells and Articular Chondrocytes to Enhance Chondrogenesis

Cited by 19 publications

References 82 publications

Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development

Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development

Bioprinting of osteochondral tissues: A perspective on current gaps and future trends

Mesenchymal Stem Cells: Potential Role in the Treatment of Osteochondral Lesions of the Ankle

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