title: Bone repair by transplantation of hTERT-immortalized human mesenchymal stem cells in mice.
abstract: BACKGROUND
  Human mesenchymal stem cells (hMSCs) are multipotent stem cells found in the adult bone marrow that have the capacity to differentiate into various mesenchymal cell types. The hMSCs may provide a potential therapy to restore damaged tissues or organs of mesenchymal origin; however, a drawback is their limited life span in vitro.
  
  
  METHODS
  We immortalized normal hMSCs with retrovirally transmitted human telomerase reverse transcriptase cDNA. One of the immortalized clones (YKNK-12) was established, and the biological characteristics were investigated in vitro and in vivo.
  
  
  RESULTS
  YKNK-12 cells were capable of differentiating adipocytes, osetoblasts, and chondrocytes. Osteogenically differentiated YKNK-12 cells produced significant levels of growth factors BMP4, BMP6, FGF6, FGF7, transforming growth factor-beta1, and transforming growth factor-beta3.. Microcomputer tomography T and soft X-ray assays showed an excellent calvarial bone healing in mice after transplantation of osteogenically differentiated YKNK-12 cells. These cells expressed human-specific osteocalcin and increased the gene expression of runt-related transcription factor 2, alkaline phosphatase, osteocalcin, and osterix in the bone regenerating area. YKNK-12 cell transplant corrected the bone defect without inducing any adverse effects.
  
  
  CONCLUSIONS
  We conclude that hMSCs immortalized by transduction with human telomerase reverse transcriptase may provide an unlimited source of cells for therapeutic use in bone regeneration.
authors: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Hiroyuki
authors: H
authors: Nakahara
authors: Haruo
authors: H
authors: Misawa
authors: Takahiro
authors: T
authors: Hayashi
authors: Eisaku
authors: E
authors: Kondo
authors: Takeshi
authors: T
authors: Yuasa
authors: Yasuhiro
authors: Y
authors: Kubota
authors: Masayuki
authors: M
authors: Seita
authors: Hironobu
authors: H
authors: Kawamoto
authors: Wael A R A
authors: WA
authors: Hassan
authors: Reham A R A
authors: RA
authors: Hassan
authors: Shahid M
authors: SM
authors: Javed
authors: Masato
authors: M
authors: Tanaka
authors: Hirosuke
authors: H
authors: Endo
authors: Hirofumi
authors: H
authors: Noguchi
authors: Shinichi
authors: S
authors: Matsumoto
authors: Katsuyoshi
authors: K
authors: Takata
authors: Yuichi
authors: Y
authors: Tashiro
authors: Shuhei
authors: S
authors: Nakaji
authors: Toshifumi
authors: T
authors: Ozaki
authors: Naoya
authors: N
authors: Kobayashi
mesh_terms: D017667:Adipocytes / Q000201:enzymology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*; D001861:Bone Regeneration; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D019902:Chondrocytes / Q000201:enzymology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000201:enzymology; D010012:Osteogenesis; D011859:Radiography; D012886:Skull / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; C509186:TERT protein, human; D019098:Telomerase