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

Ali Mobasheri; Heonsik Choi; Pablo Martín-Vasallo

doi:10.3390/biology9100330

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

Biology (Basel). 2020 Oct 9;9(10):330. doi: 10.3390/biology9100330.

Authors

Ali Mobasheri^{1

2

3

4}, Heonsik Choi^{5

6}, Pablo Martín-Vasallo⁷

Affiliations

¹ Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland.
² Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania.
³ Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
⁴ Versus Arthritis Centre for Sport, Exercise and Osteoarthritis Research, Queen's Medical Centre, Nottingham NG7 2UH, UK.
⁵ Kolon TissueGene, Inc., Rockville, MD 20850, USA.
⁶ Healthcare Research Institute, Kolon Advanced Research Center, Kolon Industries, Inc., Magok-dong, Gangseo-gu, Seoul 07793, Korea.
⁷ UD of Biochemistry and Molecular Biology, Instituto de Tecnologías Biomédicas de Canarias, Universidad de La Laguna, San Cristóbal de La Laguna, 38071 Tenerife, Spain.

Abstract

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.

Keywords: GP2-293 cells; TissueGene-C; articular cartilage; degeneration; growth factor; osteoarthritis; protein packaging cell line; protein production platform; regeneration; transforming growth factor β1 (TGF-β1).

Publication types

Review