Osteoinduction by bone morphogenetic protein 2-expressing adenoviral vector: application of biomaterial to mask the host immune response

Human Gene Therapy
Junya SonobeKazuhisa Bessho

Abstract

We constructed a human bone morphogenetic protein 2 (BMP-2)-expressing adenoviral vector, AxCABMP-2, which showed osteoinduction in immunosuppressed rats. In immunocompetent rats, new bone was not induced, because of the rapid elimination of transduced cells. Biomaterials such as collagen can be used as carriers for the delivery of DNA vectors, allowing prolonged expression of plasmid DNA in normal animals. We evaluated osteoinduction with AxCABMP-2 and atelopeptide type I collagen in immunocompetent rats. Collagen plus AxCABMP-2 (BMP group), collagen plus AxCALacZ (LacZ group), or collagen alone (CL group) was implanted into calf muscle pouches in immunocompetent rats, or AxCABMP-2 alone (injection group) was injected into the calf muscle. On days 3, 7, 14, and 21 after treatment, osteoinduction was evaluated. In the BMP group, bone formation was not observed on days 3 and 7. On day 14, radiographic formation was seen, but little bone formation was detected histologically. On day 21, new bone formation was observed both radiologically and histologically. In the other groups, osteoinduction was not found at any time. Immunohistochemical analysis on days 3 and 7 revealed decreased immunogenicity in the BMP group compared with th...Continue Reading

References

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Citations

Jan 18, 2005·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·M EgermannA W Baltzer
Mar 7, 2007·Annals of Biomedical Engineering·Malavosklish BikramJennifer L West
Apr 2, 2013·Acta Biomaterialia·Laura RoseHasan Uludağ
Dec 11, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christopher H EvansPaul D Robbins
Aug 19, 2007·Human Gene Therapy·Christine M Fouletier-DillingAlan R Davis
Feb 11, 2010·Tissue Engineering. Part B, Reviews·Gadi PelledEdward M Schwarz
May 1, 2007·Regenerative Medicine·N KimelmanD Gazit
Nov 22, 2005·Expert Opinion on Drug Delivery·Mathew VarkeyHasan Uludag
Apr 15, 2011·Injury·Christopher Evans
Mar 14, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Catherine M CowanKang Ting
Apr 5, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Laura Rose, Hasan Uludağ
Feb 9, 2017·Tissue Engineering. Part B, Reviews·Justin L MadrigalEduardo A Silva
Jun 24, 2010·Expert Reviews in Molecular Medicine·Christopher H Evans

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