Telomerase immortalized human amnion- and adipose-derived mesenchymal stem cells: maintenance of differentiation and immunomodulatory characteristics.
Cell banking of mesenchymal stem cells (SCs) from various human tissues has significantly increased the feasibility of SC-based therapies. Sources such as adipose tissue and amnion offer outstanding possibilities for allogeneic transplantation due to their high differentiation potential and their ability to modulate immune reaction. Limitations, however, concern the reduced replicative potential as a result of progressive telomere erosion, which hampers scaleable production and long-term analysis of these cells. Here we report the establishment and characterization of two human amnion-derived and two human adipose-derived SC lines immortalized by ectopic expression of the catalytic subunit of human telomerase (hTERT). hTERT overexpression resulted in continuously growing SC lines that were largely unaltered concerning surface marker profile, morphology, karyotype, and immunosuppressive capacity with similar or enhanced differentiation potential for up to 87 population doublings. While all generated lines showed equal immunomodulation compared to the parental cells, one of the amnion-derived immortalized lines resulted in significantly increased immunogenicity. Although telomerase proves as important tool for immortalizing cells, our data emphasize the need for careful and standardized characterization of each individual cell population for cell banks.
Wolbank
Susanne
S
Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria.
Stadler
Guido
G
Peterbauer
Anja
A
Gillich
Astrid
A
Karbiener
Michael
M
Streubel
Berthold
B
Wieser
Matthias
M
Katinger
Hermann
H
van Griensven
Martijn
M
Redl
Heinz
H
Gabriel
Christian
C
Grillari
Johannes
J
Grillari-Voglauer
Regina
R
D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000650:Amnion / Q000166:cytology*; D000954:Antigens, Surface / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D048430:Cell Shape; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D007621:Karyotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D009369:Neoplasms / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D047495:PPAR gamma / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D014161:Transduction, Genetic
D000954:Antigens, Surface; D007155:Immunologic Factors; D047495:PPAR gamma; D015675:Osteocalcin; D019098:Telomerase; D000469:Alkaline Phosphatase