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Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines

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Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland
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Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania
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Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
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Versus Arthritis Centre for Sport, Exercise and Osteoarthritis Research, Queen’s Medical Centre, Nottingham NG7 2UH, UK
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Kolon TissueGene, Inc., Rockville, MD 20850, USA
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Healthcare Research Institute, Kolon Advanced Research Center, Kolon Industries, Inc., Magok-dong, Gangseo-gu, Seoul 07793, Korea
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UD of Biochemistry and Molecular Biology, Instituto de Tecnologías Biomédicas de Canarias, Universidad de La Laguna, San Cristóbal de La Laguna, 38071 Tenerife, Spain
*
Author to whom correspondence should be addressed.
Biology 2020, 9(10), 330; https://doi.org/10.3390/biology9100330
Received: 27 July 2020 / Revised: 5 October 2020 / Accepted: 6 October 2020 / Published: 9 October 2020
(This article belongs to the Special Issue Biology of Osteoarthritis)
Osteoarthritis (OA) is the most common form of arthritis across the world. Most of the existing drugs for OA treat the symptoms of pain and inflammation. There are no drugs that can dure the disease. There are a number of new treatments for OA including cell therapy and gene therapy. This articles outlines the concept behind TissueGene-C, a new biological drug for OA. This new treatment includes cartilage cells mixed with a genetically modified cell line called GP2-293, which is effectively a “drug factory”, over-producing the growth factors that are important for cartilage regeneration and changing the environment inside joints. The mixture is injected into the affected knee joint. These cells are designed to be short-lived and cannot reproduce. Therefore, after they have done their job, they die and are cleared by immune cells. This is a new and modern approach to treating OA and TissueGene-C is the prototype cell therapy for OA. In the future, it is entirely possible to combine different clones of genetically engineered cells like GP2-293 that have been designed to over-produce a growth factor or biological drug with cells from the cartilage endplate of the intervertebral disc to treat degeneration in the spine.
This review article focuses on the current state-of-the-art cellular and molecular biotechnology for the over-production of clinically relevant therapeutic and anabolic growth factors. We discuss how the currently available tools and emerging technologies can be used for the regenerative treatment of osteoarthritis (OA). Transfected protein packaging cell lines such as GP-293 cells may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage regeneration. However, when irradiated with gamma or x-rays, these cells lose their capacity for replication, which makes them safe for use as a live cell component of intra-articular injections. This innovation is already here, in the form of TissueGene-C, a new biological drug that consists of normal allogeneic primary chondrocytes combined with transduced GP2-293 cells that overexpress the growth factor transforming growth factor β1 (TGF-β1). TissueGene-C has revolutionized the concept of cell therapy, allowing drug companies to develop live cells as biological drug delivery systems for direct intra-articular injection of growth factors whose half-lives are in the order of minutes. Therefore, in this paper, we discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging eukaryotic cell lines are superior to prokaryotic bacterial expression systems and are likely to have a significant impact on the development of new humanized biological growth factor therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA, especially when injected directly into the joint.
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Keywords: osteoarthritis; articular cartilage; degeneration; regeneration; growth factor; protein production platform; protein packaging cell line; transforming growth factor β1 (TGF-β1); GP2-293 cells; TissueGene-C osteoarthritis; articular cartilage; degeneration; regeneration; growth factor; protein production platform; protein packaging cell line; transforming growth factor β1 (TGF-β1); GP2-293 cells; TissueGene-C
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MDPI and ACS Style

Mobasheri, A.; Choi, H.; Martín-Vasallo, P. Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines. Biology 2020, 9, 330. https://doi.org/10.3390/biology9100330

AMA Style

Mobasheri A, Choi H, Martín-Vasallo P. Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines. Biology. 2020; 9(10):330. https://doi.org/10.3390/biology9100330

Chicago/Turabian Style

Mobasheri, Ali; Choi, Heonsik; Martín-Vasallo, Pablo. 2020. "Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines" Biology 9, no. 10: 330. https://doi.org/10.3390/biology9100330

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