Human embryonic stem cell-derived cardiovascular progenitor cells efficiently colonize in bFGF-tethered natural matrix to construct contracting humanized rat hearts

Published on Feb 1, 2018in Biomaterials10.273
· DOI :10.1016/j.biomaterials.2017.10.054
Sarah Rajabi4
Estimated H-index: 4
Sara Pahlavan6
Estimated H-index: 6
+ 8 AuthorsHossein Baharvand44
Estimated H-index: 44
Abstract Bioengineering of whole hearts using human embryonic stem cells (hESCs)-derived cardiovascular progenitor cells (CPCs) and natural matrices is a promising approach to overcome organ donor shortage threatening millions of patients awaiting for heart transplantation. Here, we developed a novel strategy for generation of heart constructs by repopulating engineered decellularized rat hearts using hESCs-derived CPCs. Careful expansion of CPCs in a scalable stirred-suspension bioreactor combined with step-wise seeding (60 million cells in 3 steps of 20 million per 1.5 h) onto decellularized hearts containing immobilized basic fibroblast growth factor (bFGF) resulted in improved retention of CPCs and differentiation to cardiomyocytes, smooth muscle cells and endothelial cells as evaluated by immunohistochemistry and qRT-PCR. We observed spontaneous and synchronous contractions of humanized hearts after 12 days of perfusion as well as advanced alignment of myofilaments. Our study provides a robust platform for generation of artificial human hearts and resolves major bottlenecks hindering further development of this technology.
  • References (51)
  • Citations (8)
📖 Papers frequently viewed together
6 Authors (Xianmei Meng, ..., Ali Nsair)
4 Citations
30 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Santiago RouraH-Index: 21
Last. Antoni Bayes-Genis (Autonomous University of Barcelona)H-Index: 43
view all 3 authors...
Fibrin is a topical haemostat, sealant and tissue glue, which consists of concentrated fibrinogen and thrombin. It has broad medical and research uses. Recently, several studies have shown that engineered patches comprising mixtures of biological or synthetic materials and progenitor cells showed therapeutic promise for regenerating damaged tissues. In that context, fibrin maintains cell adherence at the site of injury, where cells are required for tissue repair, and offers a nurturing environme...
13 CitationsSource
#1K. Breckwoldt (UHH: University of Hamburg)H-Index: 7
#2David Letuffe-Brenière (UHH: University of Hamburg)H-Index: 2
Last. HansenArne (UHH: University of Hamburg)H-Index: 25
view all 22 authors...
This protocol describes how to generate defined embryoid bodies and subsequent standardized beating engineered heart tissue from human iPSCs using small molecules.
40 CitationsSource
#1Malte TiburcyH-Index: 18
#2James E. HudsonH-Index: 14
view all 31 authors...
Background:Advancing structural and functional maturation of stem cell–derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, w...
126 CitationsSource
#1Samad Ahadian (U of T: University of Toronto)H-Index: 21
#2Locke Davenport Huyer (U of T: University of Toronto)H-Index: 7
Last. Milica Radisic (U of T: University of Toronto)H-Index: 53
view all 8 authors...
Abstract Polymer biomaterials are used to construct scaffolds in tissue engineering applications to assist in mechanical support, organization, and maturation of tissues. Given the flexibility, electrical conductance, and contractility of native cardiac tissues, it is desirable that polymeric scaffolds for cardiac tissue regeneration exhibit elasticity and high electrical conductivity. Herein, we developed a facile approach to introduce carbon nanotubes (CNTs) into poly(octamethylene maleate (an...
22 CitationsSource
#1Doris A. Taylor (The Texas Heart Institute)H-Index: 36
#2Rohan B. Parikh (The Texas Heart Institute)H-Index: 2
Last. Luiz C. Sampaio (The Texas Heart Institute)H-Index: 7
view all 3 authors...
Purpose of Review In this review, we focus on the multiple advancements in the field of cardiovascular regenerative medicine and the state-of-the art of building a heart. An organ is comprised of cells, but cells alone do not comprise an organ. We summarize the components needed, the hurdles, and likely translational steps defining the opportunities for discovery.
14 CitationsSource
Last. Antoni Bayes-Genis (Autonomous University of Barcelona)H-Index: 43
view all 10 authors...
Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI)...
11 CitationsSource
#1Bin Duan (UNMC: University of Nebraska Medical Center)H-Index: 22
3D bioprinting is a group of rapidly growing techniques that allows building engineered tissue constructs with complex and hierarchical structures, mechanical and biological heterogeneity. It enables implementation of various bioinks through different printing mechanisms and precise deposition of cell and/or biomolecule laden biomaterials in predefined locations. This review briefly summarizes applicable bioink materials and various bioprinting techniques, and presents the recent advances in bio...
82 CitationsSource
#1Hananeh FonoudiH-Index: 4
#2Hassan Ansari (University of Science and Culture)H-Index: 5
Last. Hossein Baharvand (University of Science and Culture)H-Index: 44
view all 9 authors...
Maximizing the benefit of human pluripotent stem cells (hPSCs) for research, disease modeling, pharmaceutical and clinical applications requires robust methods for the large-scale production of functional cell types, including cardiomyocytes. Here we demonstrate that the temporal manipulation of WNT, TGF-β, and SHH signaling pathways leads to highly efficient cardiomyocyte differentiation of single-cell passaged hPSC lines in both static suspension and stirred suspension bioreactor systems. Empl...
8 CitationsSource
#1Brenda M. Ogle (UMN: University of Minnesota)H-Index: 21
#2Nenad Bursac (Duke University)H-Index: 39
Last. Gordana Vunjak-Novakovic (Columbia University)H-Index: 108
view all 13 authors...
The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or “big questions” were articulated that, if addressed, could substantially advance the current state of the art in modeling heart disease and realizing heart repai...
54 CitationsSource
#1Sabine C. Den Hartogh (LEI: Leiden University)H-Index: 4
#2Katherine Wolstencroft (LEI: Leiden University)H-Index: 6
Last. Robert Passier (LEI: Leiden University)H-Index: 41
view all 4 authors...
In vitro cardiac differentiation of human pluripotent stem cells (hPSCs) closely recapitulates in vivo embryonic heart development, and therefore, provides an excellent model to study human cardiac development. We recently generated the dual cardiac fluorescent reporter MESP1mCherry/wNKX2-5eGFP/w line in human embryonic stem cells (hESCs), allowing the visualization of pre-cardiac MESP1+ mesoderm and their further commitment towards the cardiac lineage, marked by activation of the cardiac transc...
20 CitationsSource
Cited By8
#1Tzu-Cheng Sung (NCU: National Central University)H-Index: 1
#2Huan Chiao Su (NCU: National Central University)
Last. Akon HiguchiH-Index: 42
view all 7 authors...
Abstract The current differentiation process of human pluripotent stem cells (hPSCs) into cardiomyocytes to enhance the purity of hPSC-derived cardiomyocytes requires some purification processes, which are laborious processes. We developed cell sorting plates, which are prepared from coating thermoresponsive poly(N-isopropylacrylamide) and extracellular matrix proteins. After hPSCs were induced into cardiomyocytes on the thermoresponsive surface coated with laminin-521 for 15 days, the temperatu...
#1Melika Parchehbaf-Kashani (Shahid Beheshti University)H-Index: 1
#2Mohammadmajid Sepantafar (Royan Institute)H-Index: 5
Last. Sarah Rajabi (Royan Institute)H-Index: 4
view all 7 authors...
Abstract Cardiovascular diseases (CVD) are a major cause of mortality worldwide. Accessibility to heart tissue is limited due to sampling issues and lack of appropriate culture conditions. In addition, animal models are not an ideal choice for physiological, pharmacological, and fundamental evaluations in the cardiovascular field due to interspecies differences. Hence, there is an inevitable need for functional in vitro cardiac models. In this study, we have synthesized a novel electroconductive...
1 CitationsSource
#1Tzu-Cheng Sung (NCU: National Central University)H-Index: 1
#1Tzu Cheng Sung (NCU: National Central University)H-Index: 1
Last. Shih-Tien HsuH-Index: 13
view all 13 authors...
Abstract Human induced pluripotent stem cells (hiPSCs) were generated on several biomaterials from human amniotic fluid in completely xeno-free and feeder-free conditions via the transfection of pluripotent genes using a nonintegrating RNA Sendai virus vector. The effect of xeno-free culture medium on the efficiency of the establishment of human amniotic fluid stem cells from amniotic fluid was evaluated. Subsequently, the effect of cell culture biomaterials on the reprogramming efficiency was i...
1 CitationsSource
The potential of heart tissues for self-regeneration is not high and supposedly limited to a small number of the niche stem cells. This makes it extremely important to develop regenerative technologies for the myocardium based on modern techniques, for instance, cell re-programming and 3D bioprinting. However, it is often difficult to differentiate the sensational reports regularly appearing in mass media on “breakthrough” technologies from those that really have practical applications. The arti...
Cardiac Progenitor Cells (CPCs) show great potential as a cell resource for restoring cardiac function in patients affected by heart disease or heart failure. CPCs are proliferative and committed to cardiac fate, capable of generating cells of all the cardiac lineages. These cells offer a significant shift in paradigm over the use of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes owing to the latter’s inability to recapitulate mature features of a native myocardium, limiting t...
#1Tzu-Cheng Sung (WMU: Wenzhou Medical College)H-Index: 1
#2Cheng-Hui LiuH-Index: 2
Last. Akon Higuchi (NCU: National Central University)
view all 9 authors...
Current xeno-free and chemically defined methods for the differentiation of hPSCs (human pluripotent stem cells) into cardiomyocytes are not efficient and are sometimes not reproducible. Therefore, it is necessary to develop reliable and efficient methods for the differentiation of hPSCs into cardiomyocytes for future use in cardiovascular research related to drug discovery, cardiotoxicity screening, and disease modeling. We evaluated two representative differentiation methods that were reported...
#1Dhavan Sharma (MTU: Michigan Technological University)H-Index: 3
#2Morgan Ferguson (MTU: Michigan Technological University)H-Index: 1
Last. ZhaoFeng (MTU: Michigan Technological University)H-Index: 26
view all 4 authors...
Engineered cardiac patches (ECPs) hold great promise to repair ischemia-induced damages to the myocardium. Recent studies have provided robust technological advances in obtaining pure cardiac cell populations as well as various novel scaffold materials to generate engineered cardiac tissues that can significantly improve electrical and contractile functions of damaged myocardium. Given the significance in understanding the cellular and extracellular structural as well as compositional details of...
#1Tohid Rezaei Topraggaleh (TMU: Tarbiat Modares University)H-Index: 2
#2Mojtaba Rezazadeh Valojerdi (TMU: Tarbiat Modares University)H-Index: 22
Last. Hossein Baharvand (University of Science and Culture)H-Index: 44
view all 4 authors...
Extracellular matrix-derived scaffolds provide an efficient platform for the generation of organ-like structures. Successful development of testicular organoids (TOs) with the capability of supporting complete spermatogenesis has not been reported yet. Here, we have developed an optimized method for the decellularization of ram testicular tissue fragments. Our findings showed that testicular fragments treated with a serial combination of Triton X-100 and SDS in PBS for 48 h resulted in the effic...
2 CitationsSource
#1Donald Bejleri (Georgia Institute of Technology)H-Index: 2
#2Michael E. Davis (Georgia Institute of Technology)H-Index: 5
3 CitationsSource
#1Kristin M. French (UTSW: University of Texas Southwestern Medical Center)H-Index: 2
#2Michael E. Davis (Georgia Institute of Technology)H-Index: 5
Cardiovascular disease remains an extremely deadly and costly burden across the globe. Since the myocardium has a limited regenerative capacity, current therapies are restricted to pharmaceuticals, mechanical and electrical support devices, and synthetic materials. Decellularized extracellular matrices have strong potential to provide support to failing myocardium. Their native composition offers complex biochemical cues beyond what can be synthesized in the laboratory. Their physical versatilit...