University of Oulu

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.

Over-production of therapeutic growth factors for articular cartilage regeneration by protein production platforms and protein packaging cell lines

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Author: Mobasheri, Ali1,2,3,4; Choi, Heonsik5,6; Martín-Vasallo, Pablo7
Organizations: 1Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland
2Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania
3Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
4Versus Arthritis Centre for Sport, Exercise and Osteoarthritis Research, Queen’s Medical Centre, Nottingham NG7 2UH, UK
5Kolon TissueGene, Inc., Rockville, MD 20850, USA
6Healthcare Research Institute, Kolon Advanced Research Center, Kolon Industries, Inc., Magok-dong, Gangseo-gu, Seoul 07793, Korea
7UD of Biochemistry and Molecular Biology, Instituto de Tecnologías Biomédicas de Canarias, Universidad de La Laguna, San Cristóbal de La Laguna, 38071 Tenerife, Spain
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
Persistent link:
Language: English
Published: Multidisciplinary Digital Publishing Institute, 2020
Publish Date: 2020-10-28


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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Simple summary

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.

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Series: Biology
ISSN: 2079-7737
ISSN-E: 2079-7737
ISSN-L: 2079-7737
Volume: 9
Issue: 10
Article number: 330
DOI: 10.3390/biology9100330
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3111 Biomedicine
Funding: A.M. has received funding from the following sources: The European Commission Framework 7 program (EU FP7; HEALTH.2012.2.4.5-2, project number 305815; Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases). The Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework program (FP7/2007-2013) and EFPIA companies’ in-kind contribution. A.M. also wishes to acknowledge funding from the European Commission through a Marie Curie Intra-European Fellowship for Career Development grant (project number 625746; acronym: CHONDRION; FP7-PEOPLE-2013-IEF). A.M. also wishes to acknowledge financial support from the European Structural and Social Funds (ES Strukt ¯ urin˙ es Paramos) through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity “Improvement of researchers” qualification by implementing world-class R&D projects’ of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding program: Attracting Foreign Researchers for Research Implementation (2018–2022).
Copyright information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (