Chronic Optogenetic Pacing of Human-Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissues

2020 ◽  
pp. 151-169
Author(s):  
Marc Dwenger ◽  
William J. Kowalski ◽  
Hidetoshi Masumoto ◽  
Takeichiro Nakane ◽  
Bradley B. Keller
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Tissues ◽  
Induced Pluripotent

Human induced pluripotent stem cell-derived cardiac tissue on a thin collagen membrane with natural microstructures

2016 ◽  
Vol 4 (11) ◽  
pp. 1655-1662 ◽  
Author(s):  
Li Wang ◽  
Xiaoqing Zhang ◽  
Cong Xu ◽  
Hui Liu ◽  
Jianhua Qin
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Induced Pluripotent Stem Cell ◽  
Collagen Membrane ◽  
Cardiac Tissues ◽  
New Strategy ◽  
Induced Pluripotent

We present a new strategy to produce a thin collagen membrane from porcine tendons and engineered cardiac tissues using hiPSC-derived cardiomyocytes.

scholarly journals Chronic optical pacing conditioning of h-iPSC engineered cardiac tissues

2019 ◽  
Vol 10 ◽  
pp. 204173141984174 ◽  
Author(s):  
Marc Dwenger ◽  
William J Kowalski ◽  
Fei Ye ◽  
Fangping Yuan ◽  
Joseph P Tinney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Electrical Stimulation ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Induced Pluripotent Stem Cell ◽  
Mechanical Stretch ◽  
In Vitro Models ◽  
Cardiac Tissues ◽  
Induced Pluripotent

The immaturity of human induced pluripotent stem cell derived engineered cardiac tissues limits their ability to regenerate damaged myocardium and to serve as robust in vitro models for human disease and drug toxicity studies. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and/or electrical stimulation promote engineered cardiac tissue maturation but have significant technical limitations. Non-contacting chronic optical stimulation using heterologously expressed channelrhodopsin light-gated ion channels, termed optogenetics, may be an advantageous alternative to chronic invasive electrical stimulation for engineered cardiac tissue conditioning. We designed proof-of-principle experiments to successfully transfect human induced pluripotent stem cell derived engineered cardiac tissues with a desensitization resistant, chimeric channelrhodopsin protein, and then optically paced engineered cardiac tissues to accelerate maturation. We transfected human induced pluripotent stem cell engineered cardiac tissues using an adeno-associated virus packaged chimeric channelrhodopsin and then verified optically paced by whole cell patch clamp. Engineered cardiac tissues were then chronically optically paced above their intrinsic beat rates in vitro from day 7 to 14. Chronically optically paced resulted in improved engineered cardiac tissue electrophysiological properties and subtle changes in the expression of some cardiac relevant genes, though active force generation and histology were unchanged. These results validate the feasibility of a novel chronically optically paced paradigm to explore non-invasive and scalable optically paced–induced engineered cardiac tissue maturation strategies.

Use of human induced pluripotent stem cell-derived engineered cardiac tissues to predict cardiotoxic responses to a chemotherapeutic agent

2020 ◽  
Vol 105 ◽  
pp. 106821
Author(s):  
Roozbeh Aschar-Sobbi ◽  
Nicole Feric ◽  
Isabella Pallotta ◽  
Rishabh Singh ◽  
Danielle R. Bogdanowicz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Chemotherapeutic Agent ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Tissues ◽  
Induced Pluripotent

Human induced pluripotent stem cell-derived beating cardiac tissues on paper

Lab on a Chip ◽  
2015 ◽  
Vol 15 (22) ◽  
pp. 4283-4290 ◽  
Author(s):  
Li Wang ◽  
Cong Xu ◽  
Yujuan Zhu ◽  
Yue Yu ◽  
Ning Sun ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Beating Heart ◽  
Cardiac Tissues ◽  
Human Ipscs ◽  
Induced Pluripotent

We demonstrate the first attempt to differentiate human-iPSCs into cardiac microtissues on paper and create “a beating heart on paper.”

scholarly journals Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues

JTCVS Open ◽  
2021 ◽  
Author(s):  
Hiroaki Osada ◽  
Masahide Kawatou ◽  
Daiki Fujita ◽  
Yasuhiko Tabata ◽  
Kenji Minatoya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Therapeutic Potential ◽  
Induced Pluripotent Stem Cell ◽  
Clinical Grade ◽  
Cardiac Tissues ◽  
Induced Pluripotent

Abstract 14377: Therapeutic Potential of Clinical Grade Human Induced Pluripotent Stem Cell-derived Cardiac Tissues for a Rat Myocardial Infarction Model: A Pre-clinical Study for a Cell Transplantation Therapy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hiroaki Osada ◽  
Hidetoshi Masumoto ◽  
Masahide Kawatou ◽  
Tadashi Ikeda ◽  
Yasuhiko Tabata ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Left Ventricular ◽  
Clinical Grade ◽  
Cell Sheets ◽  
Cardiac Tissues ◽  
Cell Lineages ◽  
Induced Pluripotent

Introduction: Transplantation of three-dimensional bioengineered cardiac tissues composed of pluripotent stem cell-derived cardiovascular cell lineages is reported to hold potential for functional recovery on pre-clinical studies. We aimed to evaluate therapeutic and myocardial regenerative potential of clinical grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) on a rat myocardial infarction (MI) model. Methods: Clinical grade hiPSC lines established from a healthy volunteer were simultaneously differentiated into cardiovascular cell lineages. We seeded the cells on temperature responsive culture dishes to form cell sheets. HiCTs were generated by stacking 5 cell sheets with insertion of gelatin hydrogel microspheres (GHMs) to promote oxygen and nutrition supply and transplanted onto an athymic rat MI model (n=6). Echocardiography and histological analysis at 12 weeks after surgery were conducted and compared to those in animals with sham surgery (n=9) and with cell sheet stacks without GHMs [GHM(-), n=6]. Some of HiCT-transplanted rats were subjected to tissue clearing and two-photon excitation microscopy (TPEM) to assess graft vascularization. Results: Flow cytometry revealed cellular components after differentiation as follows: 52.0±1.4% of cardiomyocytes (cardiac isoform of troponin-T + :cTnT), 9.9±0.7% of vascular endothelial cells (VE-cadherin + ) and 14.1±1.8% of vascular mural cells (PDGFRβ + ). Echocardiography revealed significantly lower left ventricular end diastolic volume (LVEDV) and higher left ventricular ejection fraction (LVEF) in HiCT group [sham vs GHM(-) vs HiCT: LVEDV; 1.5±0.1 vs 1.3±0.05 vs 0.9±0.03 mL, p<0.0001 / LVEF; 59.7±2.2 vs 67.4±0.6 vs 82.7±0.9 %, p<0.0001]. HiCT group showed significantly larger engraftment [GHM(-) vs HiCT; 12 week; 0.1 ± 0.1 vs 1.8 ± 0.6 mm 2 ; p<0.05]. Engrafted graft tissues were composed of cTnT / α-Actinin-positive cardiomyocytes which exhibited obvious striated structure. TPEM revealed host to graft vascular connection at 2 weeks after HiCT transplantation. Conclusions: HiCTs derived from clinical grade hiPSC potentially serve as a stem cell-derived cellular product in cardiac regenerative therapy for foreseeable clinical applications.

Sign in / Sign up

Export Citation Format

Share Document