Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture.
Shoji SekiMami IwasakiHiroto MakinoYasuhito YaharaYoshitaka MiyazakiKatsuhiko KameiHayato FutakawaMakiko NogamiNguyen Tran Canh TungTatsuro HirokawaMamiko TsujiYoshiharu KawaguchiPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- transcription factor
- endothelial cells
- induced apoptosis
- high glucose
- stem cells
- cell cycle arrest
- single cell
- induced pluripotent stem cells
- endoplasmic reticulum stress
- cell therapy
- spinal cord
- drug induced
- extracellular matrix
- cell death
- mesenchymal stem cells
- blood brain barrier
- pi k akt
- stress induced
- energy transfer