PMID- 17236835 OWN - NLM STAT- MEDLINE DCOM- 20070607 LR - 20141120 IS - 8756-3282 (Print) IS - 1873-2763 (Linking) VI - 40 IP - 4 DP - 2007 Apr TI - Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats. PG - 931-8 AB - The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5x10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1x10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p<0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p<0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo. FAU - Hsu, W K AU - Hsu WK AD - Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, UCLA, Center for Health Sciences 76-134, 10833 LeConte Avenue, Los Angeles, CA 90095, USA. FAU - Sugiyama, O AU - Sugiyama O FAU - Park, S H AU - Park SH FAU - Conduah, A AU - Conduah A FAU - Feeley, B T AU - Feeley BT FAU - Liu, N Q AU - Liu NQ FAU - Krenek, L AU - Krenek L FAU - Virk, M S AU - Virk MS FAU - An, D S AU - An DS FAU - Chen, I S AU - Chen IS FAU - Lieberman, J R AU - Lieberman JR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070122 PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (Bmp2 protein, rat) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Recombinant Proteins) RN - 0 (Transforming Growth Factor beta) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Biomechanical Phenomena MH - Bone Marrow Cells/metabolism MH - Bone Marrow Transplantation MH - Bone Morphogenetic Protein 2 MH - Bone Morphogenetic Proteins/biosynthesis/*genetics MH - Female MH - Femur/injuries/pathology/physiology MH - Fracture Healing/*genetics MH - Gene Expression MH - *Gene Transfer Techniques MH - Green Fluorescent Proteins/biosynthesis/genetics MH - In Vitro Techniques MH - Lentivirus/genetics MH - Rats MH - Rats, Inbred Lew MH - Recombinant Proteins/biosynthesis/genetics MH - Stromal Cells/metabolism/transplantation MH - Transforming Growth Factor beta/biosynthesis/*genetics EDAT- 2007/01/24 09:00 MHDA- 2007/06/08 09:00 CRDT- 2007/01/24 09:00 PHST- 2006/07/25 00:00 [received] PHST- 2006/10/20 00:00 [revised] PHST- 2006/10/23 00:00 [accepted] PHST- 2007/01/24 09:00 [pubmed] PHST- 2007/06/08 09:00 [medline] PHST- 2007/01/24 09:00 [entrez] AID - S8756-3282(06)00790-3 [pii] AID - 10.1016/j.bone.2006.10.030 [doi] PST - ppublish SO - Bone. 2007 Apr;40(4):931-8. doi: 10.1016/j.bone.2006.10.030. Epub 2007 Jan 22.