Bone Repair by Transplantation of hTERT-Immortalized Human Mesenchymal Stem Cells in Mice
Bone Repair by Transplantation of hTERT-Immortalized Human Mesenchymal Stem Cells in Mice
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DOI：
10.1097/tp.0b013e3181ae5ba2
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发表时间：
2009-08
期刊：
影响因子：
6.2
通讯作者：
H. Nakahara;Haruo Misawa;Takahiro Hayashi;E. Kondo;Takeshi Yuasa;Yasuhiro Kubota;M. Seita;Hironobu Kawamoto;Wael Hassan;Reham A R A Hassan-Reham-A-R-A-Hassan-121641758;Shahid M Javed;Masato Tanaka;H. Endo;H. Noguchi;S. Matsumoto;K. Takata;Y. Tashiro;S. Nakaji;T. Ozaki;N. Kobayashi
中科院分区：
文献类型：
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作者：
H. Nakahara;Haruo Misawa;Takahiro Hayashi;E. Kondo;Takeshi Yuasa;Yasuhiro Kubota;M. Seita;Hironobu Kawamoto;Wael Hassan;Reham A R A Hassan-Reham-A-R-A-Hassan-121641758;Shahid M Javed;Masato Tanaka;H. Endo;H. Noguchi;S. Matsumoto;K. Takata;Y. Tashiro;S. Nakaji;T. Ozaki;N. Kobayashi
背景。人间充质干细胞 (hMSC) 是在成人骨髓中发现的多能干细胞，具有分化成各种间充质细胞类型的能力。 hMSCs可能提供一种潜在的疗法来恢复受损的间质来源的组织或器官；然而，一个缺点是它们在体外的寿命有限。方法。我们用逆转录病毒传播的人端粒酶逆转录酶 cDNA 使正常 hMSC 永生化。建立了永生化克隆（YKNK-12）之一，并进行了体外和体内生物学特性研究。结果。 YKNK-12 细胞能够分化脂肪细胞、成骨细胞和软骨细胞。成骨分化的 YKNK-12 细胞产生显着水平的生长因子 BMP4、BMP6、FGF6、FGF7、转化生长因子-1 和转化生长因子-3。微计算机断层扫描 T 和软 X 射线检测显示，移植成骨分化的 YKNK-12 细胞后，小鼠的颅骨愈合良好。这些细胞表达人类特异性骨钙素，并增加骨再生区域中runt相关转录因子2、碱性磷酸酶、骨钙素和osterix的基因表达。 YKNK-12细胞移植纠正了骨缺损，且没有引起任何不良影响。结论。我们得出的结论是，通过人端粒酶逆转录酶转导而永生化的 hMSC 可以为骨再生治疗用途提供无限的细胞来源。
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-1, and transforming growth factor-3.. 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.