Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation

Henning Madry, Greg Emkey, David Zurakowski, Stephen Trippel

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background. Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Methods. Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli β-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. Results. The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [3H]thymidine and [35S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. Conclusions. These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal.

Original languageEnglish
Pages (from-to)238-245
Number of pages8
JournalJournal of Gene Medicine
Volume6
Issue number2
DOIs
StatePublished - Feb 2004

Fingerprint

Fibroblast Growth Factor 2
Chondrocytes
Joints
Transplantation
Cell Proliferation
Complementary DNA
Articular Cartilage
Transfection
Galactosidases
Genes
Lac Operon
Glycosaminoglycans
Cytomegalovirus
Transgenes
Mitogens
Thymidine
Sulfates
Cartilage
Plasmids
Cell Culture Techniques

Keywords

  • Cartilage defects
  • Chondrocytes
  • FGF-2
  • Transfection
  • Transplantation

ASJC Scopus subject areas

  • Genetics

Cite this

Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation. / Madry, Henning; Emkey, Greg; Zurakowski, David; Trippel, Stephen.

In: Journal of Gene Medicine, Vol. 6, No. 2, 02.2004, p. 238-245.

Research output: Contribution to journalArticle

Madry, Henning ; Emkey, Greg ; Zurakowski, David ; Trippel, Stephen. / Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation. In: Journal of Gene Medicine. 2004 ; Vol. 6, No. 2. pp. 238-245.
@article{1ec80cf7dc3c40338b2ddeb64bd92ba7,
title = "Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation",
abstract = "Background. Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Methods. Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli β-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. Results. The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [3H]thymidine and [35S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. Conclusions. These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal.",
keywords = "Cartilage defects, Chondrocytes, FGF-2, Transfection, Transplantation",
author = "Henning Madry and Greg Emkey and David Zurakowski and Stephen Trippel",
year = "2004",
month = "2",
doi = "10.1002/jgm.488",
language = "English",
volume = "6",
pages = "238--245",
journal = "Journal of Gene Medicine",
issn = "1099-498X",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation

AU - Madry, Henning

AU - Emkey, Greg

AU - Zurakowski, David

AU - Trippel, Stephen

PY - 2004/2

Y1 - 2004/2

N2 - Background. Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Methods. Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli β-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. Results. The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [3H]thymidine and [35S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. Conclusions. These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal.

AB - Background. Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Methods. Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli β-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. Results. The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [3H]thymidine and [35S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. Conclusions. These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal.

KW - Cartilage defects

KW - Chondrocytes

KW - FGF-2

KW - Transfection

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=4644244444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644244444&partnerID=8YFLogxK

U2 - 10.1002/jgm.488

DO - 10.1002/jgm.488

M3 - Article

VL - 6

SP - 238

EP - 245

JO - Journal of Gene Medicine

JF - Journal of Gene Medicine

SN - 1099-498X

IS - 2

ER -