title: Carbon nanotube-based substrates promote cardiogenesis in brown adipose-derived stem cells via β1-integrin-dependent TGF-β1 signaling pathway.
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.
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Sun
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Mou
authors.affiliation: Department of Cardiology, The General Hospital of Chinese People's Armed Police Forces, Beijing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
authors.forename: Zi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: Duval
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, People's Republic of China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, People's Republic of China.
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Dai
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, People's Republic of China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, People's Republic of China.
authors.forename: Fuzhou
authors.initials: F
authors.lastname: Tian
keywords: TGF-β1; brown adipose-derived stem cells; carbon nanotube; cardiomyocytes; β1-integrin