Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture

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 repre...

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Published in:International journal of molecular sciences 2022-04, Vol.23 (7), p.4059
Main Authors: Seki, Shoji, Iwasaki, Mami, Makino, Hiroto, Yahara, Yasuhito, Miyazaki, Yoshitaka, Kamei, Katsuhiko, Futakawa, Hayato, Nogami, Makiko, Tran Canh Tung, Nguyen, Hirokawa, Tatsuro, Tsuji, Mamiko, Kawaguchi, Yoshiharu
Format: Article
Language:English
Subjects:
alginate beads
Back pain
Back surgery
Cartilage
Cell culture
Cell differentiation
Collagen
Cooperation
Culture
Degeneration
Degenerative disc disease
direct reprogramming
Ectopic expression
Fibroblasts
Fibroblasts - metabolism
Flow cytometry
Gene expression
Genotype & phenotype
human dermal fibroblast
Humans
Intervertebral Disc - metabolism
Intervertebral Disc Degeneration - metabolism
Intervertebral Disc Degeneration - therapy
intervertebral disc disease
Intervertebral Disc Displacement
intervertebral disc regeneration
Intervertebral discs
Joint surgery
KLF4 protein
Myc protein
Nuclei (cytology)
Nucleus pulposus
Nucleus Pulposus - metabolism
nucleus pulposus cell
Phenotypes
Proteins
Regenerative medicine
Safranin-O
Sox9 protein
Stem cells
Transcription factors
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Summary: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 , , , , , and 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23074059