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Carbon nanotube-based substrates promote cardiogenesis in brown adipose-derived stem cells via β1-integrin-dependent TGF-β1 signaling pathway

Authors Sun H, Mou Y, Li Y, Li X, Chen Z, Duval K, Huang Z, Dai R, Tang L, Tian F

Received 5 June 2016

Accepted for publication 21 July 2016

Published 6 September 2016 Volume 2016:11 Pages 4381—4395

DOI https://doi.org/10.2147/IJN.S114357

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


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Hongyu Sun,1,* Yongchao Mou,2,* Yi Li,3,* Xia Li,4,* Zi Chen,2 Kayla Duval,2 Zhu Huang,1 Ruiwu Dai,1 Lijun Tang,1 Fuzhou Tian1

1Department of General Surgery, Chengdu Military General Hospital, Chengdu, People’s Republic of China; 2Thayer School of Engineering, Dartmouth College, Hanover, NH, USA; 3Department of Cardiology, The General Hospital of Chinese People’s Armed Police Forces, Beijing, People’s Republic of China; 4Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People’s Republic of China

*These authors contributed equally to this work

Abstract: Stem cell-based therapy remains one of the promising approaches for cardiac repair and regeneration. However, its applications are restricted by the limited efficacy of cardiac differentiation. To address this issue, we examined whether carbon nanotubes (CNTs) would provide an instructive extracellular microenvironment to facilitate cardiogenesis in brown adipose-derived stem cells (BASCs) and to elucidate the underlying signaling pathways. In this study, we systematically investigated a series of cellular responses of BASCs due to the incorporation of CNTs into collagen (CNT-Col) substrates that promoted cell adhesion, spreading, and growth. Moreover, we found that CNT-Col substrates remarkably improved the efficiency of BASCs cardiogenesis by using fluorescence staining and quantitative real-time reverse transcription-polymerase chain reaction. Critically, CNTs in the substrates accelerated the maturation of BASCs-derived cardiomyocytes. Furthermore, the underlying mechanism for promotion of BASCs cardiac differentiation by CNTs was determined by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction, and Western blotting assay. It is notable that β1-integrin-dependent TGF-β1 signaling pathway modulates the facilitative effect of CNTs in cardiac differentiation of BASCs. Therefore, it is an efficient approach to regulate cardiac differentiation of BASCs by the incorporation of CNTs into the native matrix. Importantly, our findings can not only facilitate the mechanistic understanding of molecular events initiating cardiac differentiation in stem cells, but also offer a potentially safer source for cardiac regenerative medicine.

Keywords:
carbon nanotube, brown adipose-derived stem cells, cardiomyocytes, TGF-β1, β1-integrin

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