Cardiac differentiation potential of human induced pluripotent stem cells in a 3D self-assembling peptide scaffold

被引:16
作者
Puig-Sanvicens, Veronica A. C. [1 ,2 ,3 ]
Semino, Carlos E. [3 ]
zur Nieden, Nicole I. [1 ,2 ]
机构
[1] Univ Calif Riverside, Coll Nat & Agr Sci, Dept Cell Biol, Riverside, CA 92521 USA
[2] Univ Calif Riverside, Coll Nat & Agr Sci, Neurosci & Stem Cell Ctr, Riverside, CA 92521 USA
[3] Univ Ramon Llull, Sch Engn, Inst Quim Sarria, Lab Tissue Engn,Dept Bioengn, Barcelona, Spain
关键词
Cardiogenesis; Human induced pluripotent stem cells; Ascorbic acid; 3D culture; Cardiac progenitor stage; RAD16-I; MOUSE EMBRYONIC FIBROBLASTS; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; CARDIOMYOCYTE DIFFERENTIATION; MYOBLAST TRANSPLANTATION; DEFINED FACTORS; ISCHEMIC CARDIOMYOPATHY; RAT HEARTS; IN-VITRO; TISSUE;
D O I
10.1016/j.diff.2015.11.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In the past decade, various strategies for cardiac reparative medicine involving stem cells from multiple sources have been investigated. However, the intra-cardiac implantation of cells with contractile ability may seriously disrupt the cardiac syncytium and de-synchronize cardiac rhythm. For this reason, bioactive cardiac implants, consisting of stem cells embedded in biomaterials that act like band aids, have been exploited to repair the cardiac wall after myocardial infarction. For such bioactive implants to function properly after transplantation, the choice of biomaterial is equally important as the selection of the stem cell source. While adult stem cells have shown promising results, they have various disadvantages including low proliferative potential in vitro, which make their successful usage in human transplants difficult. As a first step towards the development of a bioactive cardiac patch, we investigate here the cardiac differentiation properties of human induced pluripotent stem cells (hiPSCs) when cultured with and without ascorbic acid (AA) and when embedded in RAD16-I, a biomaterial commonly used to develop cardiac implants. In adherent cultures and in the absence of RAD16-I, AA promotes the cardiac differentiation of hiPSCs by enhancing the expression of specific cardiac genes and proteins and by increasing the number of contracting clusters. In turn, embedding in peptide hydrogel based on RAD16-I interferes with the normal cardiac differentiation progression. Embedded hiPSCs up-regulate genes associated with early cardiogenesis by up to 105 times independently of the presence of AA. However, neither connexin 43 nor troponin I proteins, which are related with mature cardiomyocytes, were detected and no contraction was noted in the constructs. Future experiments will need to focus on characterizing the mature cardiac phenotype of these cells when implanted into infarcted myocardia and assess their regenerative potential in vivo. (C)) 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:101 / 110
页数:10
相关论文
共 58 条
[1]   Cardiovascular Disease Risk Assessment and Prevention Current Guidelines and Limitations [J].
Alagona, Peter, Jr. ;
Ahmad, Tariq Ali .
MEDICAL CLINICS OF NORTH AMERICA, 2015, 99 (04) :711-+
[2]   Evidence that human cardiac myocytes divide after myocardial infarction (Publication with Expression of Concern. See vol. 379, pg. 1870, 2018) [J].
Beltrami, AP ;
Urbanek, K ;
Kajstura, J ;
Yan, SM ;
Finato, N ;
Bussani, R ;
Nadal-Ginard, B ;
Silvestri, F ;
Leri, A ;
Beltrami, CA ;
Anversa, P .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (23) :1750-1757
[3]   Adult cardiac stem cells are multipotent and support myocardial regeneration [J].
Beltrami, AP ;
Barlucchi, L ;
Torella, D ;
Baker, M ;
Limana, F ;
Chimenti, S ;
Kasahara, H ;
Rota, M ;
Musso, E ;
Urbanek, K ;
Leri, A ;
Kajstura, J ;
Nadal-Ginard, B ;
Anversa, P .
CELL, 2003, 114 (06) :763-776
[4]   Adipose-derived stem cells: Isolation, expansion and differentiation [J].
Bunnell, Bruce A. ;
Flaat, Mette ;
Gagliardi, Christine ;
Patel, Bindiya ;
Ripoll, Cynthia .
METHODS, 2008, 45 (02) :115-120
[5]  
Burridge PW, 2014, NAT METHODS, V11, P855, DOI [10.1038/NMETH.2999, 10.1038/nmeth.2999]
[6]  
Bussmann BM, 2013, J TISSUE ENG REGEN M
[7]   Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells [J].
Cao, Nan ;
Liu, Zumei ;
Chen, Zhongyan ;
Wang, Jia ;
Chen, Taotao ;
Zhao, Xiaoyang ;
Ma, Yu ;
Qin, Lianju ;
Kang, Jiuhong ;
Wei, Bin ;
Wang, Liu ;
Jin, Ying ;
Yang, Huang-Tian .
CELL RESEARCH, 2012, 22 (01) :219-236
[8]  
Castells-Sala C, 2012, IEEE ENG MED BIO, P5658, DOI 10.1109/EMBC.2012.6347278
[9]   Creating the bioartificial myocardium for cardiac repair: challenges and clinical targets [J].
Chachques, Juan C. ;
Pradas, Manuel Monleon ;
Bayes-Genis, Antoni ;
Semino, Carlos .
EXPERT REVIEW OF CARDIOVASCULAR THERAPY, 2013, 11 (12) :1701-1711
[10]   Transfecting and Nucleofecting Human Induced Pluripotent Stem Cells [J].
Chatterjee, Papri ;
Cheung, Yuri ;
Liew, Chee .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2011, (56)