title: Characterization and biodistribution of human mesenchymal stem cells transduced with lentiviral-mediated BMP2.
abstract: Recently, the genetic modification of mesenchymal stem cells (MSCs) has led to increased differentiation potential. For the therapeutic application of genetically modified MSCs, it is crucial to evaluate their characteristics and safety. In this study, we investigated the effects of bone morphogenetic protein 2 (BMP2) gene transfer on the characteristics and biodistribution of human MSCs. Lentiviral-mediated BMP2 transduction to MSCs enhanced osteocyte differentiation and decreased adipocyte differentiation. Although there is no significant difference in cell proliferation capacity, MSCs transduced BMP2 proliferate somewhat higher than nontransduced or GFP transduced MSCs. No significant changes were observed in surface antigen expression in genetically modified MSCs. In vivo transplantation of lentiviral-mediated BMP2 gene transferred MSCs to nude mice did not result in tumor formation. To evaluate the biodistribution of genetically modified cells, MSCs carrying BMP2 were injected into the tail vein of femur fractured mice. The introduced MSCs were detected in the spleen, testis and fractured femur 28 days post-implantation. These findings suggest that diverse safety tests for genetically modified MSCs should be considered, particularly when a lentivirus mediated gene transfer method is used.
authors.affiliation: Department of Pharmaceuticals and Medical Devices Research, National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Seoul, 122-704, Korea.
authors.forename: Kyoung Suk
authors.initials: KS
authors.lastname: Choi
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Ahn
authors.forename: Tek Seung
authors.initials: TS
authors.lastname: Kim
authors.forename: Jiseon
authors.initials: J
authors.lastname: Kim
authors.forename: Byoung-Guk
authors.initials: BG
authors.lastname: Kim
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Han
authors.forename: Sang Ja
authors.initials: SJ
authors.lastname: Ban
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Youngju
authors.initials: Y
authors.lastname: Choi
authors.forename: Chul-Joo
authors.initials: CJ
authors.lastname: Lim
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005264:Femoral Fractures / Q000601:surgery; D005434:Flow Cytometry; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins