An immortalized human adipose-derived stem cell line with highly enhanced chondrogenic properties
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An immortalized human adipose-derived stem cell line with highly enhanced chondrogenic properties. / Katz, Dakota B.; Huynh, Nguyen P.T.; Savadipour, Alireza; Palte, Ilan; Guilak, Farshid.
In: Biochemical and Biophysical Research Communications, Vol. 530, No. 1, 2020, p. 252-258.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - An immortalized human adipose-derived stem cell line with highly enhanced chondrogenic properties
AU - Katz, Dakota B.
AU - Huynh, Nguyen P.T.
AU - Savadipour, Alireza
AU - Palte, Ilan
AU - Guilak, Farshid
PY - 2020
Y1 - 2020
N2 - Human adipose-derived stem cells (ASCs) are a commonly used cell type for cartilage tissue engineering. However, donor-to-donor variability, cell heterogeneity, inconsistent chondrogenic potential, and limited expansion potential can hinder the use of these cells for modeling chondrogenesis, in vitro screening of drugs and treatments for joint diseases, or translational applications for tissue engineered cartilage repair. The goal of this study was to create an immortalized ASC line that showed enhanced and consistent chondrogenic potential for applications in cartilage tissue engineering as well as to provide a platform for investigation of biological and mechanobiological pathways involved in cartilage homeostasis and disease. Starting with the ASC52telo cell line, a hTERT-immortalized ASC line, we used lentivirus to overexpress SOX9, a master regulator of chondrogenesis, and screened several clonal populations of SOX9 overexpressing cells to form a new stable cell line with high chondrogenic potential. One clonal line, named ASC52telo-SOX9, displayed increased GAG and type II collagen synthesis and was found to be responsive to both mechanical and inflammatory stimuli in a manner similar to native chondrocytes. The development of a clonal line such as ASC52telo-SOX9 has the potential to be a powerful tool for studying cartilage homeostasis and disease mechanisms in vitro, and potentially as a platform for in vitro drug screening for diseases that affect articular cartilage. Our findings provide an approach for the development of other immortalized cell lines with improved chondrogenic capabilities in ASCs or other adult stem cells.
AB - Human adipose-derived stem cells (ASCs) are a commonly used cell type for cartilage tissue engineering. However, donor-to-donor variability, cell heterogeneity, inconsistent chondrogenic potential, and limited expansion potential can hinder the use of these cells for modeling chondrogenesis, in vitro screening of drugs and treatments for joint diseases, or translational applications for tissue engineered cartilage repair. The goal of this study was to create an immortalized ASC line that showed enhanced and consistent chondrogenic potential for applications in cartilage tissue engineering as well as to provide a platform for investigation of biological and mechanobiological pathways involved in cartilage homeostasis and disease. Starting with the ASC52telo cell line, a hTERT-immortalized ASC line, we used lentivirus to overexpress SOX9, a master regulator of chondrogenesis, and screened several clonal populations of SOX9 overexpressing cells to form a new stable cell line with high chondrogenic potential. One clonal line, named ASC52telo-SOX9, displayed increased GAG and type II collagen synthesis and was found to be responsive to both mechanical and inflammatory stimuli in a manner similar to native chondrocytes. The development of a clonal line such as ASC52telo-SOX9 has the potential to be a powerful tool for studying cartilage homeostasis and disease mechanisms in vitro, and potentially as a platform for in vitro drug screening for diseases that affect articular cartilage. Our findings provide an approach for the development of other immortalized cell lines with improved chondrogenic capabilities in ASCs or other adult stem cells.
KW - Collagen
KW - Interleukin 1
KW - Mesenchymal stem cell
KW - MSC
KW - Proteoglycan
KW - TRPV4
U2 - 10.1016/j.bbrc.2020.07.016
DO - 10.1016/j.bbrc.2020.07.016
M3 - Journal article
C2 - 32828295
AN - SCOPUS:85088943036
VL - 530
SP - 252
EP - 258
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -
ID: 248932358