Different forms of tenascin-C with tenascin-r regulate neural differentiation in bone marrow-derived human mesenchymal stem cells

Hung Li Tsai, Wen Ta Chiu, Chia Lang Fang, Shiaw Min Hwang, Perry F. Renshaw, Wen Fu Thomas Lai

研究成果: 雜誌貢獻文章

18 引文 斯高帕斯(Scopus)

摘要

Mesenchymal stem cells (MSCs) are currently thought to transdifferentiate into neural lineages under specific microenvironments. Studies have reported that the tenascin family members, tenascin-C (TnC) and tenascin-R (TnR), regulate differentiation and migration, in addition to neurite outgrowth and survival in numerous types of neurons and mesenchymal progenitor cells. However, the mechanisms by which TnC and TnR affect neuronal differentiation are not well understood. In this study, we hypothesized that different forms of tenascin might regulate the neural transdifferentiation of human bone marrow-derived mesenchymal stem cells. Human MSCs were cultured in media incorporated with soluble tenascins, or on precoated tenascins. In a qualitative polymerase chain reaction analysis, adding a soluble TnC and TnR mixture to the medium significantly enhanced the expression of neuronal and glial markers, whereas no synaptic markers were expressed. Conversely, in groups of cells treated with coated TnC, hMSCs showed neurite outgrowth and synaptic marker expression. After being treated with coated TnR, hMSCs exhibited neuronal differentiation; however, it inhibited neurite outgrowth and synaptic marker expression. A combination of TnC and TnR significantly promoted hMSC differentiation in neurons or oligodendrocytes, induced neurite formation, and inhibited differentiation into astrocytes. Furthermore, the effect of the tenascin mixture showed dose-dependent effects, and a mixture ratio of 1:1 to 1:2 (TnC:TnR) provided the most obvious differentiation of neurons and oligodendrocytes. In a functional blocking study, integrin α7 and α9β1-blocking antibodies inhibited, respectively, 80% and 20% of mRNA expression by hMSCs in the coated tenascin mixture. In summary, the coated combination of TnC and TnR appeared to regulate neural differentiation signaling through integrin α7 and α9β1 in bone marrow-derived hMSCs. Our findings demonstrate novel mechanisms by which tenascin regulates neural differentiation, and enable the use of cell therapy to treat neurodegenerative diseases.

原文英語
頁(從 - 到)1908-1921
頁數14
期刊Tissue Engineering - Part A
20
發行號13-14
DOIs
出版狀態已發佈 - 七月 1 2014

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

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