Improved cartilage regeneration utilizing mesenchymal stem cells in TGF-beta1 gene-activated scaffolds.

Recently, bone marrow-derived mesenchymal stem cells (MSCs) have been paid more attention for cartilage regeneration. This study evaluated the potential of using MSCs seeded in plasmid transforming growth factor beta1 (pTGF-beta1)-activated three-dimensional chitosan/gelatin scaffolds for improving cartilage repair in vivo. Significant cell proliferation and transforming growth factor beta1 protein expression were observed in vitro in pTGFbeta1-activated scaffolds. Transforming growth factor beta1-activated scaffolds showed high collagen type II and aggrecan expression and low collagen type I expression during in vitro cultivation. MSC-based pTGF-beta1-activated scaffolds also exhibited cartilage histology with high secretion of collagen type II in vitro under the stimulation of pTGF-beta1. In rabbits with full-thickness cartilage defects, the implantation of MSC-based pTGF-beta1-activated scaffolds not only significantly promoted chondrogenic differentiation of MSCs and hyalin-like cartilage matrix synthesis, but also remarkably improved the overall repair of rabbit cartilage defects and exhibited favorable tissue integrity at 10 weeks postsurgery. These results suggest that MSC-based localized pTGF-beta1-activated scaffolds have potential applications for in vivo cartilage repair.

[1]  B. A. Byers,et al.  Transient exposure to transforming growth factor beta 3 under serum-free conditions enhances the biomechanical and biochemical maturation of tissue-engineered cartilage. , 2008, Tissue engineering. Part A.

[2]  Jiake Xu,et al.  Gene expression profiles of human chondrocytes during passaged monolayer cultivation , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[3]  Wan-Ju Li,et al.  Mold-shaped, nanofiber scaffold-based cartilage engineering using human mesenchymal stem cells and bioreactor. , 2008, The Journal of surgical research.

[4]  K. Takagi,et al.  The chondrogenic repair response of undifferentiated mesenchymal cells in rat full-thickness articular cartilage defects. , 2008, Osteoarthritis and cartilage.

[5]  Francis Berenbaum,et al.  Primary culture and phenotyping of murine chondrocytes , 2008, Nature Protocols.

[6]  D. Chan,et al.  In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration. , 2008, Biomaterials.

[7]  Bruce Caterson,et al.  The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study. , 2008, Tissue engineering. Part A.

[8]  Rocky S Tuan,et al.  Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells. , 2008, Arthritis and rheumatism.

[9]  T. Taguchi,et al.  Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model , 2008, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[10]  T. Ishii,et al.  Repair of large full‐thickness articular cartilage defects by transplantation of autologous uncultured bone‐marrow‐derived mononuclear cells , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  J. Dragoo,et al.  Healing full-thickness cartilage defects using adipose-derived stem cells. , 2007, Tissue engineering.

[12]  Antonios G. Mikos,et al.  Injectable biodegradable hydrogel composites for rabbit marrow mesenchymal stem cell and growth factor delivery for cartilage tissue engineering. , 2007, Biomaterials.

[13]  M. Hyttinen,et al.  Poly-L-D-lactic acid scaffold in the repair of porcine knee cartilage lesions. , 2007, Tissue engineering.

[14]  T. Trzaska,et al.  Articular cartilage defects: study of 25,124 knee arthroscopies. , 2007, The Knee.

[15]  Heungsoo Shin,et al.  Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. , 2007, Advanced drug delivery reviews.

[16]  M. Spector,et al.  Collagen scaffolds for nonviral IGF-1 gene delivery in articular cartilage tissue engineering , 2007, Gene Therapy.

[17]  Chueh Shangkai,et al.  Transplantation of allogeneic chondrocytes cultured in fibroin sponge and stirring chamber to promote cartilage regeneration. , 2007, Tissue engineering.

[18]  J. Jansen,et al.  Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair. , 2007, Osteoarthritis and cartilage.

[19]  Glenn D Prestwich,et al.  Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. , 2006, Tissue engineering.

[20]  Harrie Weinans,et al.  Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFβ2 and FGF2 , 2006 .

[21]  Hisatoshi Kobayashi,et al.  Combination of 3D tissue engineered scaffold and non-viral gene carrier enhance in vitro DNA expression of mesenchymal stem cells. , 2006, Biomaterials.

[22]  H. Diao,et al.  Gene-Activated Matrices for Cartilage Defect Reparation , 2006 .

[23]  P. Brooks.  The burden of musculoskeletal disease—a global perspective , 2006, Clinical Rheumatology.

[24]  Yasuhiko Tabata,et al.  Enhanced ectopic bone formation using a combination of plasmid DNA impregnation into 3-D scaffold and bioreactor perfusion culture. , 2006, Biomaterials.

[25]  Zhi Ding,et al.  Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-beta1 for chondrocytes proliferation. , 2006, Biomaterials.

[26]  Y. Tabata,et al.  Perfusion culture enhances osteogenic differentiation of rat mesenchymal stem cells in collagen sponge reinforced with poly(glycolic Acid) fiber. , 2005, Tissue engineering.

[27]  K. Takagi,et al.  One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits. , 2004, Osteoarthritis and cartilage.

[28]  A. Nixon,et al.  Gene-based approaches for the repair of articular cartilage , 2004, Gene Therapy.

[29]  M. Menger,et al.  Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid‐mediated gene transfer in a gel suspension delivery system , 2003, The journal of gene medicine.

[30]  M. Rudert.  Histological Evaluation of Osteochondral Defects: Consideration of Animal Models with Emphasis on the Rabbit, Experimental Setup, Follow-Up and Applied Methods , 2002, Cells Tissues Organs.

[31]  Q. Shang,et al.  Repairing large porcine full-thickness defects of articular cartilage using autologous chondrocyte-engineered cartilage. , 2002, Tissue engineering.

[32]  E B Hunziker,et al.  Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. , 2002, Osteoarthritis and cartilage.

[33]  B. Olsen,et al.  Delivery of plasmid DNA to articular chondrocytes via novel collagen-glycosaminoglycan matrices. , 2002, Human gene therapy.

[34]  E. Wagner,et al.  Reaching a genetic and molecular understanding of skeletal development. , 2002, Developmental cell.

[35]  W. Puhl,et al.  Lipofection of rabbit chondrocytes and long lasting expression of a lacZ reporter system in alginate beads. , 2002, Osteoarthritis and cartilage.

[36]  E. Hunziker,et al.  Delamination rates of tissue flaps used in articular cartilage repair , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[37]  S. O’Driscoll.  Current Concepts Review - The Healing and Regeneration of Articular Cartilage* , 1998 .

[38]  S D Gillogly,et al.  Treatment of articular cartilage defects of the knee with autologous chondrocyte implantation. , 1998, The Journal of orthopaedic and sports physical therapy.

[39]  C. Sledge,et al.  Histological Evaluation of the Course of Healing of Canine Articular Cartilage Defects Treated with Cultured Autologous Chondrocytes , 1998 .

[40]  E. Yelin,et al.  Special article the economic cost and social and psychological impact of musculoskeletal conditions , 1995 .

[41]  D Amiel,et al.  Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. , 1995, Journal of biomedical materials research.

[42]  James D. Kang,et al.  Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction. , 2005, The spine journal : official journal of the North American Spine Society.

[43]  V Vécsei,et al.  Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. , 2002, Osteoarthritis and cartilage.

[44]  A. Klibanov,et al.  Protein stability in controlled-release systems , 2000, Nature Biotechnology.

[45]  A M Mackay,et al.  Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. , 1998, Tissue engineering.

[46]  R. Mayne,et al.  Collagen types IX and X in the developing chick tibiotarsus: analyses of mRNAs and proteins. , 1991, Development.