Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture |
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| Authors: | Shoji Seki Mami Iwasaki Hiroto Makino Yasuhito Yahara Yoshitaka Miyazaki Katsuhiko Kamei Hayato Futakawa Makiko Nogami Nguyen Tran Canh Tung Tatsuro Hirokawa Mamiko Tsuji Yoshiharu Kawaguchi |
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| Affiliation: | 1.Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan; (M.I.); (H.M.); (K.K.); (H.F.); (M.N.); (N.T.C.T.); (T.H.); (M.T.); (Y.K.);2.Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan;3.KUBIX Inc., ha8-1 Netsuno, Hakusan 920-2161, Japan;4.Department of Trauma and Orthopaedic Surgery, Vietnam Military Medical University, Hanoi 100000, Vietnam |
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| Abstract: | 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. |
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| Keywords: | intervertebral disc disease human dermal fibroblast nucleus pulposus cell alginate beads direct reprogramming intervertebral disc regeneration induced pluripotent stem cells |
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