Invossa™ (TISSUEGENE-C) induces an anti-inflammatory environment in the arthritic knee joints via macrophage polarization

Choi, Kyoung-Baek; Lee, H.; Kim, D.; Kim, M.; Lim, Chae-Lyul; Lee, Y.-J.; Lee, B.; Kim, S.; Lee, M.; Choi, Hwanjun

doi:10.1016/j.joca.2017.02.267

Cited by 5 publications

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“…PRP is known to provide an anti-inflammatory and potentially pain-reducing effect in patients with knee OA. 11 , 23 , 27 , 49 , 63 The presence of various pro-chondrogenic growth factors suggests it may have a potential to regenerate cartilage, but this has not been proven to consistently or significantly occur in an all patients. 6 , 12 , 17 , 47 , 57 Zilretta, an FDA-approved, extended-release TCA, may also provide a superior reduction in pain and inflammation compared with traditional glucocorticoid injections.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β is an anti-inflammatory cytokine that when expressed controls chondrocyte proliferation and differentiation, as well as ECM accumulation. 11 As a result of this process, TGF-β has been identified as a major player in maintaining the structural integrity and overall health of articular cartilage. 35 Therefore, TGF-β is considered as a primary cytokine in restoring articular cartilage that has been damaged.…”

Section: T Issue G Ene -C Ia In...mentioning

confidence: 99%

“…TissueGene-C (TissueGene) is an IA injection genetic therapy developed for the treatment of primary OA. 11 Its components include allogeneic chondrocytes and irradiated GP2-293 cells overexpressing TGF-β, mixed in a 3:1 ratio. The irradiation process prevents postinjection proliferation of the modified TGF-β–expressing chondrocytes and maintains the 3:1 ratio by preventing proliferation of the transplanted cells.…”

Section: T Issue G Ene -C Ia In...mentioning

confidence: 99%

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A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections

Raghuram

Agyare

Thipaphay

et al. 2023

Orthopaedic Journal of Sports Medicine

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Background: The pathology of primary osteoarthritis (OA) begins with structural cartilage damage, which initiates a self-propagating inflammatory pathway that further exacerbates cartilage deterioration. Current standard of care for knee primary OA involves treating the inflammatory symptoms to manage pain, which includes intra-articular (IA) injections of cortisone, an anti-inflammatory steroid, followed by a series of joint-cushioning hyaluronic acid gel injections. However, these injections do not delay the progression of primary OA. More focus on the underlying cellular pathology of OA has prompted researchers to develop treatments targeting the biochemical mechanisms of cartilage degradation. Purpose: Researchers have yet to develop a United States Food and Drug Administration (FDA)–approved injection that has been demonstrated to significantly regenerate damaged articular cartilage. This paper reviews the current research on experimental injections aimed at achieving cellular restoration of the hyaline cartilage tissue of the knee joint. Study Design: Narrative review. Methods: The authors conducted a narrative literature review examining studies on primary OA pathogenesis and a systematic review of non–FDA-approved IA injections for the treatment of primary OA of the knee, described as “disease-modifying osteoarthritis drugs” in phase 1, 2, and 3 clinical trials. Conclusion: New treatment approaches for primary OA investigate the potential of genetic therapies to restore native cartilage. It is clear that the most promising IA injections that could improve treatment of primary OA are bioengineered advanced-delivery steroid-hydrogel preparations, ex vivo expanded allogeneic stem cell injections, genetically engineered chondrocyte injections, recombinant fibroblast growth factor therapy, injections of selective proteinase inhibitors, senolytic therapy via injections, injectable antioxidant therapies, injections of Wnt pathway inhibitors, injections of nuclear factor–kappa β inhibitors, injections of modified human angiopoietin-like–3, various potential viral vector–based genetic therapy approaches, and RNA genetic technology administered via injections.

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Section: Discussionmentioning

confidence: 99%

Section: T Issue G Ene -C Ia In...mentioning

confidence: 99%

Section: T Issue G Ene -C Ia In...mentioning

confidence: 99%

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A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections

Raghuram

Agyare

Thipaphay

et al. 2023

Orthopaedic Journal of Sports Medicine

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“…Based on this, reprogramming of Mj polarization has become the focus of research. Reprogramming intra-articular Mjs from M1 to M2 by local or systemic delivery of bioactive factors was confirmed to be able to improve the microenvironment of OA to some extent (38,39). The traditional method of Mj reprogramming involves changing the polarity of signaling molecules (such as cytokines, receptor agonists, and inhibitory antibodies).…”

Section: Discussionmentioning

confidence: 99%

Engineered M2a macrophages for the treatment of osteoarthritis

Liang

Xia

et al. 2022

Front. Immunol.

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BackgroundMacrophage is a central regulator of innate immunity. Its M2 subsets, such as interstitial synovial macrophages, have been found to play critical roles in suppressing chronic inflammation and maintaining homeostasis within the joint. These macrophages have great potential as a disease-modifying cell therapy for osteoarthritis (OA). However, this has not yet been studied.MethodsMacrophages were isolated from the bone marrow of rats. We constructed a stable macrophage that “locked” in anti-inflammatory and pro-regenerative M2a polarity (L-M2a) by simultaneously knocking out tumor necrosis factor receptor 1 (TNFR1) and overexpressing IL-4 using Cas9-ribonuclear proteins (Cas9-RNP) and electroporation. In vitro, these L-M2a macrophages were treated with OA synovial fluid or co-cultured with OA chondrocytes or fibroblast-like synoviocytes (FLS). In vivo, L-M2a macrophages were injected intra-articularly to evaluate their homing and engrafting abilities and therapeutic effects on OA progression using a rat model.ResultsL-M2a macrophages displayed a typical anti-inflammatory phenotype similar to that of M2 macrophages in vitro. In OA microenvironment, L-M2a macrophages maintained a stable anti-inflammatory phenotype, whereas unmodified M2 macrophages lost their phenotype and switched to M1 polarity. L-M2a macrophages demonstrated a potent anti-inflammatory effect in crosstalk with OA-FLSs and an anti-degenerative effect in crosstalk with senescent OA chondrocytes. In vivo, compared with M2 macrophages and exosomes, L-M2a macrophages exhibited significantly superior therapeutic effects in OA by successfully resolving inflammation, restoring tissue homeostasis, and promoting cartilage regeneration.ConclusionThe engineered L-M2a macrophages maintained a superior anti-inflammatory and pro-regenerative capacity in the inflammatory OA microenvironment and represents an ideal new strategy for the disease-modifying therapy of OA.

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“…What’s more, several studies have investigated the underlying molecular mechanisms in the effectiveness of Invossa on OA. The majority of studies suggest that Invossa provides an anti-inflammatory surroundings in the arthritic knee joints by means of macrophage polarization which is crucial for modifying the disease (Choi et al, 2017; Lee et al, 2018).…”

Section: Human Cell-based Gene Therapy Productsmentioning

confidence: 99%

Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders

et al. 2019

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The field of gene therapy is striving more than ever to define a path to the clinic and the market. Twenty gene therapy products have already been approved and over two thousand human gene therapy clinical trials have been reported worldwide. These advances raise great hope to treat devastating rare and inherited diseases as well as incurable illnesses. Understanding of the precise pathomechanisms of diseases as well as the development of efficient and specific gene targeting and delivery tools are revolutionizing the global market. Currently, human cancers and monogenic disorders are indications number one. The elevated prevalence of genetic disorders and cancers, clear gene manipulation guidelines and increasing financial support for gene therapy in clinical trials are major trends. Gene therapy is presently starting to become commercially profitable as a number of gene and cell-based gene therapy products have entered the market and the clinic. This article reviews the history and development of twenty approved human gene and cell-based gene therapy products that have been approved up-to-now in clinic and markets of mainly North America, Europe and Asia.

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Invossa™ (TISSUEGENE-C) induces an anti-inflammatory environment in the arthritic knee joints via macrophage polarization

Cited by 5 publications

References 0 publications

A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections

A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections

Engineered M2a macrophages for the treatment of osteoarthritis

Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders

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