| Autor: |
Yuelin Zhang, Zhao Zhang, Peikai Chen, Chui Yan Ma, Cheng Li, Tiffany Y.K. Au, Vivian Tam, Yan Peng, Ron Wu, Kenneth Man Chee Cheung, Pak C. Sham, Hung-fat Tse, Danny Chan, Victor Y. Leung, Kathryn S.E. Cheah, Qizhou Lian |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 30, Iss 8, Pp 2791-2806.e5 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2020.01.100 |
| Popis: |
Summary: Intervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-β pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration. : Zhang et al. report notochord-like and nucleus pulposus (NP)-like cells can be derived from human pluripotent stem cells using a NOTO-eGFP reporter system and a compound-defined protocol. These derived NP-like cells share high similarities with adolescent human NP cells and attenuate injury-induced intervertebral disc degeneration after transplantation. Keywords: human induced pluripotent stem cells, intervertebral disc disease, nucleus pulposus (NP)-like cells, notochord-like cells (NCLs), directed differentiation |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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