TY - JOUR
T1 - Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines
AU - Mobasheri, Ali
AU - Choi, Heonsik
AU - Martín-Vasallo, Pablo
N1 - Funding Information:
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 Struktūrinės 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).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10/9
Y1 - 2020/10/9
N2 - 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.
AB - 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.
KW - Articular cartilage
KW - Degeneration
KW - GP2‐293 cells
KW - Growth factor
KW - Osteoarthritis
KW - Protein packaging cell line
KW - Protein production platform
KW - Regeneration
KW - TissueGene‐C
KW - Transforming growth factor β1 (TGF‐β1)
UR - http://www.scopus.com/inward/record.url?scp=85092350151&partnerID=8YFLogxK
U2 - 10.3390/biology9100330
DO - 10.3390/biology9100330
M3 - Review article
C2 - 33050357
SN - 2079-7737
VL - 9
SP - 1
EP - 19
JO - Biology
JF - Biology
IS - 10
M1 - 330
ER -