title: The role of transduced bone marrow cells overexpressing BMP-2 in healing critical-sized defects in a mouse femur.
abstract: The role that transduced mouse bone marrow stromal cells (mBMSCs) engineered to overexpress human bone morphogenetic protein 2 (BMP-2) play in healing critical-sized skeletal defects is largely unknown. We evaluated the interaction between host osteoprogenitor cells and donor mBMSCs transduced with either a lentiviral (LV) vector-expressing red fluorescent protein (RFP) with or without BMP-2 that were implanted into a critical-sized femoral defect. Radiographs taken at the time of killing were evaluated using a five-point scaled scoring system. Frozen histologic sections were analyzed to assess both the transduced cells' role in bone repair and the local osteoprogenitor response. There was complete radiographic bridging in 94% of group I (LV-RFPch-BMP-2-cmyc) and 100% of group III (recombinant human BMP-2) specimens. Radiographs demonstrated a lack of healing in group II (LV-RFPch). Mouse BMSCs transduced with an LV-RFPch-BMP-2 vector were able to induce host cells to differentiate down an osteoblastic lineage and heal a critical-sized defect. However, the donor cells appeared to be functioning as a delivery vehicle of BMP-2 rather than actually differentiating into osteoblasts capable of participating in bone repair as evidenced by a lack of colocalization of the transduced cells to the sites of skeletal repair where the host progenitor cells were found.
authors: Department of Orthopaedic Surgery, Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors: M
authors: M
authors: Pensak
authors: Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, USA.
authors: S
authors: S
authors: Hong
authors: Department of Orthopaedic Surgery, Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors: A
authors: A
authors: Dukas
authors: Department of Orthopaedic Surgery, Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors: B
authors: B
authors: Tinsley
authors: Department of Orthopaedic Surgery, Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors: H
authors: H
authors: Drissi
authors: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: A
authors: A
authors: Tang
authors: Department of Orthopaedic Surgery, Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors: M
authors: M
authors: Cote
authors: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: O
authors: O
authors: Sugiyama
authors: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors: A
authors: A
authors: Lichtler
authors: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors: D
authors: D
authors: Rowe
authors: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: J R
authors: JR
authors: Lieberman
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001861:Bone Regeneration; D002478:Cells, Cultured; D005269:Femur / Q000166:cytology* / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D013977:Tibia / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2