Bone repair by transplantation of hTERT-immortalized human mesenchymal stem cells in mice

Hiroyuki Nakahara, Haruo Misawa, Takahiro Hayashi, Eisaku Kondo, Takeshi Yuasa, Yasuhiro Kubota, Masayuki Seita, Hironobu Kawamoto, Wael A.R.A. Hassan, Reham A.R.A. Hassan, Shahid M. Javed, Masato Tanaka, Hirosuke Endo, Hirofumi Noguchi, Shinichi Matsumoto, Katsuyoshi Takata, Yuichi Tashiro, Shuhei Nakaji, Toshifumi Ozaki, Naoya Kobayashi

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29 Citations (Scopus)

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-β1, and transforming growth factor-β3.. 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.

Original languageEnglish
Pages (from-to)346-353
Number of pages8
JournalTransplantation
Volume88
Issue number3
DOIs
Publication statusPublished - Aug 15 2009

Keywords

  • Bone marrow
  • Mesenchymal stem cells
  • hTERT

ASJC Scopus subject areas

  • Transplantation

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    Nakahara, H., Misawa, H., Hayashi, T., Kondo, E., Yuasa, T., Kubota, Y., Seita, M., Kawamoto, H., Hassan, W. A. R. A., Hassan, R. A. R. A., Javed, S. M., Tanaka, M., Endo, H., Noguchi, H., Matsumoto, S., Takata, K., Tashiro, Y., Nakaji, S., Ozaki, T., & Kobayashi, N. (2009). Bone repair by transplantation of hTERT-immortalized human mesenchymal stem cells in mice. Transplantation, 88(3), 346-353. https://doi.org/10.1097/TP.0b013e3181ae5ba2