Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation

H. Madry, D. Zurakowski, Stephen Trippel

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage. Transfection of articular chondrocytes with an expression plasmid vector containing the cDNA for human IGF-I under the control of the cytomegalovirus promoter/enhancer led to expression of the transgene and synthesis of biologically relevant amounts of IGF-I protein. Transplantation of transfected articular chondrocytes on to the surface of articular cartilage explants led to the formation of a new tissue layer on the cartilage explant surface. The new tissue was characterized by the presence of type II collagen and proteoglycan and by the absence of type I collagen, consistent with hyaline-like cartilage. The tissue formed by the chondrocytes expressing IGF-I was thicker and contained more cells than controls transfected with an expression plasmid vector containing the Escherichia coli (E. coli) β-galactosidase (lacZ) gene. Transplantation of articular chondrocytes that overexpress human IGF-I also increased DNA synthesis and the synthesis of glycosaminoglycans by the underlying explant cartilage chondrocytes. These results identify a mechanism by which IGF-I may simultaneously promote chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data further suggest that therapeutic growth factor gene transfer may be applicable to articular cartilage.

Original languageEnglish (US)
Pages (from-to)1443-1449
Number of pages7
JournalGene Therapy
Volume8
Issue number19
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Chondrocytes
Insulin-Like Growth Factor I
Joints
Transplantation
Cartilage
Articular Cartilage
Plasmids
Galactosidases
Hyaline Cartilage
Chondrogenesis
Lac Operon
Collagen Type II
Proteoglycans
Collagen Type I
Glycosaminoglycans
Cytomegalovirus
Transgenes
Transfection
Intercellular Signaling Peptides and Proteins
Homeostasis

Keywords

  • Cartilage
  • Cell transplantation
  • Chondrocytes
  • Gene transfer
  • IGF-I

ASJC Scopus subject areas

  • Genetics

Cite this

Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation. / Madry, H.; Zurakowski, D.; Trippel, Stephen.

In: Gene Therapy, Vol. 8, No. 19, 2001, p. 1443-1449.

Research output: Contribution to journalArticle

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