title: Influence of insulin-like growth factor I overexpression via recombinant adeno-associated vector gene transfer upon the biological activities and differentiation potential of human bone marrow-derived mesenchymal stem cells.
abstract: BACKGROUND
  The transplantation of genetically modified progenitor cells such as bone marrow-derived mesenchymal stem cells (MSCs) is an attractive strategy to improve the natural healing of articular cartilage defects. In the present study, we examined the potential benefits of sustained overexpression of the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) via gene transfer upon the biological activities of human MSCs (hMSCs).
  
  
  METHODS
  Recombinant adeno-associated vectors (rAAV) were used to deliver a human IGF-I coding sequence in undifferentiated and chondrogenically-induced primary hMSCs in order to determine the efficacy and duration of transgene expression and the subsequent effects of the genetic modification upon the chondrogenic versus osteogenic differentiation profiles of the cells relative to control (lacZ) treatment after 21 days in vitro.
  
  
  RESULTS
  Significant and prolonged expression of IGF-I was evidenced in undifferentiated and most importantly in chondrogenically-induced hMSCs transduced with the candidate rAAV-hIGF-I vector for up to 21 days, leading to enhanced proliferative, biosynthetic, and chondrogenic activities compared with rAAV-lacZ treatment. Overexpression of IGF-I as achieved in the conditions applied here also increased the expression of hypertrophic and osteogenic markers in the treated cells.
  
  
  CONCLUSIONS
  These results suggest that a tight regulation of rAAV expression may be necessary for further translation of the approach in clinically relevant animal models in vivo. However, the current findings support the concept of using this type of vector as an effective tool to treat articular cartilage defects via gene- and stem cell-based procedures.
authors.forename: Janina
authors.initials: J
authors.lastname: Frisch
authors.forename: Jagadeesh Kumar
authors.initials: JK
authors.lastname: Venkatesan
authors.forename: Ana
authors.initials: A
authors.lastname: Rey-Rico
authors.forename: Gertrud
authors.initials: G
authors.lastname: Schmitt
authors.forename: Henning
authors.initials: H
authors.lastname: Madry
authors.forename: Magali
authors.initials: M
authors.lastname: Cucchiarini
mesh_terms: D002358:Cartilage, Articular / Q000473:pathology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D019076:Transgenes
chemical_list: D011498:Protein Precursors; D011994:Recombinant Proteins; C119953:pro-insulin-like growth factor I; D007334:Insulin-Like Growth Factor I