Autor: |
Chen, Jialin, Zhang, Erchen, Zhang, Wei, Liu, Zeyu, Lu, Ping, Zhu, Ting, Yin, Zi, Backman, Ludvig J., Liu, Huanhuan, Chen, Xiao, Ouyang, Hongwei |
Zdroj: |
Stem Cells Translational Medicine; November 2017, Vol. 6 Issue: 11 p2009-2019, 11p |
Abstrakt: |
Stem cells have been widely used in tendon tissue engineering. The lack of refined and controlled differentiation strategy hampers the tendon repair and regeneration. This study aimed to find new effective differentiation factors for stepwise tenogenic differentiation. By microarray screening, the transcript factor Foswas found to be expressed in significantly higher amounts in postnatal Achilles tendon tissue derived from 1 day as compared with 7‐days‐old rats. It was further confirmed that expression of Fosdecreased with time in postnatal rat Achilles tendon, which was accompanied with the decreased expression of multiply tendon markers. The expression of Fosalso declined during regular in vitro cell culture, which corresponded to the loss of tendon phenotype. In a cell‐sheet and a three‐dimensional cell culture model, the expression of Foswas upregulated as compared with in regular cell culture, together with the recovery of tendon phenotype. In addition, significant higher expression of tendon markers was found in Fos‐overexpressed tendon stem/progenitor cells (TSPCs), and Fosknock‐down gave opposite results. In situ rat tendon repair experiments found more normal tendon‐like tissue formed and higher tendon markers expression at 4 weeks postimplantation of Fos‐overexpressed TSPCs derived nonscaffold engineering tendon (cell‐sheet), as compared with the control group. This study identifies Fosas a new marker and functional driver in the early stage teno‐lineage differentiation of tendon, which paves the way for effective stepwise tendon differentiation and future tendon regeneration. StemCellsTranslationalMedicine2017;6:2009–2019 Overexpression of Fosin tendon stem/progenitor cells (TSPCs) caused upregulated gene expression of tendon markers. (A): Gene expression of Fos. (B, C): Gene expression of multiply tendon markers. The expression level of each gene in TSPCs‐M group was set as 1. *, p< .05; **, p< .01. Abbreviations: TSPCs‐fo: TSPCs transfected with Fos;TSPCs‐M: control group which is transfected with green fluorescence protein. |
Databáze: |
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