Alterations of MEK1/2-ERK1/2, IFNγ and Smad2/3 associated Signalling pathways during cryopreservation of ASCs affect their differentiation towards VSMC-like cells - ScienceDirect

Stem Cell Research

Craig A. Simmons^1,2,3¹  J. Paul Santerre^1,3²  Xiaoqing Zhang^1³ 

[1] Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, Ontario M5S 3G8, Canada^2;Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario M5G 1G6, Canada^3;Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Institute of Biomaterials and Biomedical Engineering, University of Toronto, 661 University Avenue, 14th floor, Toronto, Ontario M5G 1M1, Canada^1

关键词: ASC;    Adipose derived stromal cells;    α-SMA;    α-smooth muscle actin.;    CA;    Cryopreserved ASCs.;    FA;    Fresh ASCs.;    IFNγ;    Interferon gamma.;    NE;    Norepinephrine.;    RA;    Retinoic acid.;    SM22α;    Smooth muscle 22α.;    SMMHC;    Smooth muscle myosin heavy chain.;    TEVG;    Tissue engineered vascular grafts.;    TNFα;    Tumor necrosis factor alpha.;    TGF-β1;    Transforming growth factor-β1.;    UASMC;    Umbilical artery smooth muscle cells.;    VSMC;    Vascular smooth muscle cells.;    Vaso;    Vasopressin.;    Adipose derived stromal cells;    Vascular smooth muscle cell differentiation;    Cryopreservation;    Smoothelin;    Interferon gamma;    Extracellular signal regulated kinase;   

DOI  :  10.1016/j.scr.2018.09.005

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

Vascular smooth muscle cells (VSMCs) play essential roles in regulating blood vessel form and function and they are required for vascular tissue regeneration. Multipotent adipose derived stromal cells (ASCs) can be differentiated into VSMC-like cells, which can be used as a potential VSMC source for the development of vascular tissue. However, the effects of cryopreservation on the differentiation of ASCs towards VSMCs are poorly studied to date. This study compared fresh ASCs (FA) vs. cryopreserved ASCs (CA) with respect to their differentiation potential towards VSMC-like cells. The expression of contractile VSMC markers (such as smoothelin) and cell contractility were investigated. It was found that VSMC-like cells derived from CA expressed smoothelin gene and protein at lower levels and showed compromised contractility in response to vasoconstrictors, when compared with those derived from FA. Moreover, it was demonstrated that this negative effect of cryopreservation could be mediated by MEK1/2-ERK1/2, IFNγ and Smad2/3 associated Signalling pathways. Treatment of CA with MEK1/2-ERK1/2 activator or IFNγ neutralizing antibodies enhanced Smad2/3 phosphorylation and showed a rescue of the negative effect of cryopreservation on the differentiation of ASCs towards VSMC-like cells. These findings are important for defining approaches that may use cryopreserved ASCs for vascular tissue regeneration.

【 授权许可】

Unknown