title: Biodistribution and in vivo efficacy of genetically modified human mesenchymal stem cells systemically transplanted into a mouse bone fracture model.
abstract: Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical application due to their ability to undergo multi-lineage differentiation. Recently, ex vivo genetic modification of hMSCs was attempted to increase their differentiation potential. The present study was conducted to evaluate the biodistribution and in vivo efficacy of genetically modified hMSCs. To accomplish this, Runx2, which is a key transcription factor associated with osteoblast differentiation, was transduced into hMSCs using lentiviral vectors expressing green fluorescent protein (GFP) or luciferase. Here, we developed an experimental fracture in mice femur to investigate the effects of Runx2-transduced hMSCs on bone healing and migration into injury site. We conducted bio-luminescence imaging (BLI) using luciferase-tagged vector and quantitative real-time PCR using GFP probe to investigate the biodistribution of Runx2-transduced hMSCs in the fracture model. The biodistribution of hMSC cells in the fractured femur was observed at 14 days post-transplantation upon both BLI imaging and real-time PCR. Moreover, the fractured mice transplanted with Runx2-transduced hMSCs showed superior bone healing when compared to mock-transduced hMSC and MRC5 fibroblasts which were used as control. These data suggested that transplanted genetically modified hMSCs systemically migrate to the fractured femur, where they contribute to bone formation in vivo.
authors.affiliation: Biotechnological Development Assistance Team, National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chengwon-gun, Chungcheongbuk-do 363-700, Republic of Korea. jwkang3@gmail.com
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Kang
authors.forename: Ki Dae
authors.initials: KD
authors.lastname: Park
authors.forename: Youngju
authors.initials: Y
authors.lastname: Choi
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Baek
authors.forename: Wan-Seob
authors.initials: WS
authors.lastname: Cho
authors.forename: Mina
authors.initials: M
authors.lastname: Choi
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Kyoung Suk
authors.initials: KS
authors.lastname: Choi
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Tae Moo
authors.initials: TM
authors.lastname: Yoo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005269:Femur / Q000293:injuries* / Q000378:metabolism; D050723:Fractures, Bone / Q000235:genetics* / Q000378:metabolism / Q000601:surgery*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution / Q000502:physiology