Biological characterization of long-term cultured human mesenchymal stem cells.
Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical applications. The reason is that they may have the plasticity needed to differentiate into multiple lineages and the ability to expand ex vivo. For the therapeutic applications of hMSCs to be of practical use, it is crucial to assess the efficacy and safety of hMSCs in long-term ex vivo expansion. In this study, we cultured hMSCs by population doubling (PD) 60, and investigated their growth, osteogenic and adipogenic differential abilities, change of surface markers, telomerase activity, telomere length, and gene expression related to tumorigenesis. An in vivo tumorigenesis assay was also carried out. In long-term expanded hMSCs, the cells became aged above PD 30 and their adipogenic and osteogenic differentiation potential decreased. Telomerase activity unchanged whereas telomere length decreased and karyotypes were not changed. Gene expressions related to tumorigenesis decreased in proportion as the PD of hMSCs increased. In vivo transplantation of long-term cultured hMSCs to nude mice did not result in tumor formation. These findings suggest that diverse tests for cellular therapy should be considered during the ex vivo culture of hMSCs, particularly when a prolonged and extended propagation period is required.
Kim
Jiseon
J
Pharmacological Research Department, National Institute of Toxicological Research, Korea Food & Drug Administration, Seoul, 122-704, Korea.
Kang
Jin Wook
JW
Park
Jae Hyun
JH
Choi
Youngju
Y
Choi
Kyung Suk
KS
Park
Ki Dae
KD
Baek
Dae Hyun
DH
Seong
Su Kyoung
SK
Min
Hong-Ki
HK
Kim
Hyung Soo
HS
D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010011:Osteocytes / Q000502:physiology; D010641:Phenotype; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D013997:Time Factors
D019098:Telomerase