Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells.
We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCs retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT+Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells.
Zhang
Xiaohong
X
Division of Cell Processing, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Soda
Yasushi
Y
Takahashi
Kenji
K
Bai
Yuansong
Y
Mitsuru
Ayako
A
Igura
Koichi
K
Satoh
Hitoshi
H
Yamaguchi
Satoru
S
Tani
Kenzaburo
K
Tojo
Arinobu
A
Takahashi
Tsuneo A
TA
D002454:Cell Differentiation; D002461:Cell Line, Transformed / Q000166:cytology* / Q000378:metabolism; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D019942:Genes, p16; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000166:cytology*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014161:Transduction, Genetic
C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; C509186:TERT protein, human; D019098:Telomerase