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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/4059 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shoji Seki |
| collection | DOAJ |
| description | 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 <i>MYC</i>, <i>KLF4</i>, <i>NOTO</i>, <i>SOX5</i>, <i>SOX6</i>, and <i>SOX9</i> 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. |
| first_indexed | 2024-03-09T11:44:07Z |
| format | Article |
| id | doaj.art-079e904c22bd4bd8b0f290ce8de83fbd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:44:07Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-079e904c22bd4bd8b0f290ce8de83fbd2023-11-30T23:26:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01237405910.3390/ijms23074059Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D CultureShoji Seki0Mami Iwasaki1Hiroto Makino2Yasuhito Yahara3Yoshitaka Miyazaki4Katsuhiko Kamei5Hayato Futakawa6Makiko Nogami7Nguyen Tran Canh Tung8Tatsuro Hirokawa9Mamiko Tsuji10Yoshiharu Kawaguchi11Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanKUBIX Inc., ha8-1 Netsuno, Hakusan 920-2161, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama 930-0194, JapanIntervertebral 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 <i>MYC</i>, <i>KLF4</i>, <i>NOTO</i>, <i>SOX5</i>, <i>SOX6</i>, and <i>SOX9</i> 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.https://www.mdpi.com/1422-0067/23/7/4059intervertebral disc diseasehuman dermal fibroblastnucleus pulposus cellalginate beadsdirect reprogrammingintervertebral disc regeneration |
| spellingShingle | 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 Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture International Journal of Molecular Sciences intervertebral disc disease human dermal fibroblast nucleus pulposus cell alginate beads direct reprogramming intervertebral disc regeneration |
| title | Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture |
| title_full | Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture |
| title_fullStr | Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture |
| title_full_unstemmed | Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture |
| title_short | Direct Reprogramming and Induction of Human Dermal Fibroblasts to Differentiate into iPS-Derived Nucleus Pulposus-like Cells in 3D Culture |
| title_sort | direct reprogramming and induction of human dermal fibroblasts to differentiate into ips derived nucleus pulposus like cells in 3d culture |
| topic | intervertebral disc disease human dermal fibroblast nucleus pulposus cell alginate beads direct reprogramming intervertebral disc regeneration |
| url | https://www.mdpi.com/1422-0067/23/7/4059 |
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