Literature DB >> 11300748

High-efficiency non-viral transfection of primary chondrocytes and perichondrial cells for ex-vivo gene therapy to repair articular cartilage defects.

R S Goomer1, L J Deftos, R Terkeltaub, T Maris, M C Lee, F L Harwood, D Amiel.   

Abstract

BACKGROUND: Primary perichondrial cells and chondrocytes have been used to repair articular cartilage defects in tissue engineering studies involving various animal models. Transfection of these cells with a gene that induces chondrocytic phenotype may form an ideal method to affect tissue engineering of articular cartilage.
DESIGN: A protocol for high-efficiency transfection of primary perichondrial and cartilage cells was optimized. Plasmids carrying the marker beta-galactosidase (beta-gal), PTHrP and TGF-beta1 genes driven by a strong mammalian promoter were transfected into primary perichondrial cells and chondrocytes. A three-step method was used to achieve high efficiency of transfection: (1) permeabilization of primary cells using a mild detergent, (2) association of plasmid DNAs with a polycationic (poly-l-lysine) core covalently linked to a receptor ligand (transferrin), (3) introduction of cationic liposomes to form the quaternary complex. For in-vivo assessment, polylactic acid (PLA) scaffolds seeded with beta-gal transfected perichondrial cells were implanted into experimentally created osteochondral defects in rabbit knees for 1 week.
RESULTS: The efficiency of transfection was determined to be over 70%in vitro. The transformed cells continued to express beta-gal, in vivo for the entire test period of 7 days. Furthermore, primary perichondrial cells transfected with TGF-beta1 and PTHrP over-expressed their cognate gene products.
CONCLUSION: The ability to transfect autologous primary perichondrial cells and chondrocytes with high efficiency using a non-viral system may form a first step towards tissue engineering with these transformed cells to repair articular cartilage defects. Copyright 2001 OsteoArthritis Research Society International.

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Year:  2001        PMID: 11300748     DOI: 10.1053/joca.2000.0382

Source DB:  PubMed          Journal:  Osteoarthritis Cartilage        ISSN: 1063-4584            Impact factor:   6.576


  5 in total

1.  Optimizing the generation of stable neuronal cell lines via pre-transfection restriction enzyme digestion of plasmid DNA.

Authors:  Grant Stuchbury; Gerald Münch
Journal:  Cytotechnology       Date:  2010-04-28       Impact factor: 2.058

Review 2.  Orthopedic gene therapy in 2008.

Authors:  Christopher H Evans; Steven C Ghivizzani; Paul D Robbins
Journal:  Mol Ther       Date:  2008-12-09       Impact factor: 11.454

Review 3.  Clinical potential and challenges of using genetically modified cells for articular cartilage repair.

Authors:  Henning Madry; Magali Cucchiarini
Journal:  Croat Med J       Date:  2011-06       Impact factor: 1.351

Review 4.  Gene Therapy for Cartilage Repair.

Authors:  Henning Madry; Patrick Orth; Magali Cucchiarini
Journal:  Cartilage       Date:  2011-07       Impact factor: 4.634

Review 5.  Non-viral Gene Delivery Methods for Bone and Joints.

Authors:  Benjamin Gantenbein; Shirley Tang; Julien Guerrero; Natalia Higuita-Castro; Ana I Salazar-Puerta; Andreas S Croft; Amiq Gazdhar; Devina Purmessur
Journal:  Front Bioeng Biotechnol       Date:  2020-11-19
  5 in total

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