Use of a chimeric adenovirus vector enhances BMP2 production and bone formation

Elizabeth A. Olmsted-Davis, Zbigniew Gugala, Francis H. Gannon, Patricia Yotnda, Robert E. McAlhany, Ronald W. Lindsey, Alan R. Davis

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Recombinant adenoviral vectors have potential for the treatment of a variety of musculoskeletal defects and such gene therapy systems have been a recent research focus in orthopedic surgery. In studies reported here, two different adenovirus vectors have been compared for their ability to transduce human bone marrow mesenchymal stem cells (hBM-MSCs) and elicit bone formation in vivo. Vectors consisted either of standard adenovirus type 5 (Ad5) vector or a chimeric adenovirus type 5 vector that contains an adenovirus type 35 fiber (Ad5F35), which has been recently demonstrated to bestow a different cellular tropism, and a complete cDNA encoding human bone morphogenetic 2 (BMP2). Studies were also conducted to compare the transduction efficiency of these vectors using enhanced green fluorescent protein (GFP). hBM-MSCs transduced with Ad5F35 vectors had higher levels of transgene expression than those transduced with Ad5 vectors. The results also demonstrate that hBM-MSCs lack the coxsackie-adenovirus receptor (CAR), which is responsible for cellular adsorption of Ad5. Therefore, the data suggest that Ad5 virus adsorption to hBM-MSCs is inefficient. Ad5BMP2- or Ad5F35BMP2-transduced hBM-MSCs were also compared in an in vivo heterotopic bone formation assay. Mineralized bone was radiologically identified only in muscle that received the Ad5F35BMP2 transduced hBM-MSCs. In summary, Ad5F35BMP2 can efficiently transduce hBM-MSCs leading to enhanced bone formation in vivo.

Original languageEnglish (US)
Pages (from-to)1337-1347
Number of pages11
JournalHuman Gene Therapy
Volume13
Issue number11
DOIs
StatePublished - Sep 27 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Olmsted-Davis, E. A., Gugala, Z., Gannon, F. H., Yotnda, P., McAlhany, R. E., Lindsey, R. W., & Davis, A. R. (2002). Use of a chimeric adenovirus vector enhances BMP2 production and bone formation. Human Gene Therapy, 13(11), 1337-1347. https://doi.org/10.1089/104303402760128568