TY - JOUR
T1 - Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture
AU - Seki, Shoji
AU - Iwasaki, Mami
AU - Makino, Hiroto
AU - Yahara, Yasuhito
AU - Miyazaki, Yoshitaka
AU - Kamei, Katsuhiko
AU - Futakawa, Hayato
AU - Nogami, Makiko
AU - Tung, Nguyen Tran Canh
AU - Hirokawa, Tatsuro
AU - Tsuji, Mamiko
AU - Kawaguchi, Yoshiharu
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Intervertebral disc (IVD) diseases are common spinal disorders that cause neck or back pain in the presence or absence of an underlying neurological disorder. IVD diseases develop on the basis of degeneration, and there are no established treatments for degeneration. IVD diseases may therefore represent a candidate for the application of regenerative medicine, potentially employing normal human dermal fibroblasts (NHDFs) induced to differentiate into nucleus pulposus (NP) cells. Here, we used a three-dimensional culture system to demonstrate that ectopic expression of MYC, KLF4, NOTO, SOX5, SOX6, and SOX9 in NHDFs generated NP-like cells, detected using Safranin-O staining. Quantitative PCR, microarray analysis, and fluorescence-activated cell sorting revealed that the induced NP cells exhibited a fully differentiated phenotype. These findings may significantly contribute to the development of effective strategies for treating IVD diseases.
AB - Intervertebral disc (IVD) diseases are common spinal disorders that cause neck or back pain in the presence or absence of an underlying neurological disorder. IVD diseases develop on the basis of degeneration, and there are no established treatments for degeneration. IVD diseases may therefore represent a candidate for the application of regenerative medicine, potentially employing normal human dermal fibroblasts (NHDFs) induced to differentiate into nucleus pulposus (NP) cells. Here, we used a three-dimensional culture system to demonstrate that ectopic expression of MYC, KLF4, NOTO, SOX5, SOX6, and SOX9 in NHDFs generated NP-like cells, detected using Safranin-O staining. Quantitative PCR, microarray analysis, and fluorescence-activated cell sorting revealed that the induced NP cells exhibited a fully differentiated phenotype. These findings may significantly contribute to the development of effective strategies for treating IVD diseases.
KW - alginate beads
KW - direct reprogramming
KW - human dermal fibroblast
KW - induced pluripotent stem cells
KW - intervertebral disc disease
KW - intervertebral disc regeneration
KW - nucleus pulposus cell
UR - http://www.scopus.com/inward/record.url?scp=85127599560&partnerID=8YFLogxK
U2 - 10.3390/ijms23074059
DO - 10.3390/ijms23074059
M3 - 学術論文
C2 - 35409417
AN - SCOPUS:85127599560
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 7
M1 - 4059
ER -