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 language | English |
|---|---|
| Pages (from-to) | 346-353 |
| Number of pages | 8 |
| Journal | Transplantation |
| Volume | 88 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Aug 15 2009 |
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Keywords
- Bone marrow
- hTERT
- Mesenchymal stem cells
ASJC Scopus subject areas
- Transplantation
Cite this
Bone repair by transplantation of hTERT-immortalized human mesenchymal stem cells in mice. / Nakahara, Hiroyuki; Misawa, Haruo; Hayashi, Takahiro; Kondo, Eisaku; Yuasa, Takeshi; Kubota, Yasuhiro; Seita, Masayuki; Kawamoto, Hironobu; Hassan, Wael A R A; Hassan, Reham A R A; Javed, Shahid M.; Tanaka, Masato; Endo, Hirosuke; Noguchi, Hirofumi; Matsumoto, Shinichi; Takata, Katsuyoshi; Tashiro, Yuichi; Nakaji, Shuhei; Ozaki, Toshihumi; Kobayashi, Naoya.
In: Transplantation, Vol. 88, No. 3, 15.08.2009, p. 346-353.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bone repair by transplantation of hTERT-immortalized human mesenchymal stem cells in mice
AU - Nakahara, Hiroyuki
AU - Misawa, Haruo
AU - Hayashi, Takahiro
AU - Kondo, Eisaku
AU - Yuasa, Takeshi
AU - Kubota, Yasuhiro
AU - Seita, Masayuki
AU - Kawamoto, Hironobu
AU - Hassan, Wael A R A
AU - Hassan, Reham A R A
AU - Javed, Shahid M.
AU - Tanaka, Masato
AU - Endo, Hirosuke
AU - Noguchi, Hirofumi
AU - Matsumoto, Shinichi
AU - Takata, Katsuyoshi
AU - Tashiro, Yuichi
AU - Nakaji, Shuhei
AU - Ozaki, Toshihumi
AU - Kobayashi, Naoya
PY - 2009/8/15
Y1 - 2009/8/15
N2 - 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.
AB - 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.
KW - Bone marrow
KW - hTERT
KW - Mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=69449095008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69449095008&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3181ae5ba2
DO - 10.1097/TP.0b013e3181ae5ba2
M3 - Article
C2 - 19667936
AN - SCOPUS:69449095008
VL - 88
SP - 346
EP - 353
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 3
ER -