Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
2.6
3.4
Journals
JPM
Special Issues
Pluripotent Stem Cells for Cardiac Differentiation and Disease Modeling
share announcement

Pluripotent Stem Cells for Cardiac Differentiation and Disease Modeling

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (10 November 2021) | Viewed by 9771

Special Issue Editor

Prof. Dr. Robert Passier

E-Mail Website
Guest Editor
Department of Applied Stem Cell Technologies, University of Twente, 7500 AE Enschede, The Netherlands
Interests: cardiac myocytes; pluripotent stem cells; stem cells; in vitro techniques; human embryonic stem cells; genes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular disease is responsible for the highest mortality rate worldwide and its incidence is expected to increase to epidemic proportions in the coming years and decades. Although current animal and in vitro models have broadened and deepened our insights into cardiac development and disease and their underlying mechanisms, the situation regarding the discovery of new drugs and novel therapeutic approaches is deplorable. There is a clear urgent need for academia as well as industry to create and implement human-based models that accurately mimic cardiovascular disease and have the potential to include patient-to-patient variations. Since the groundbreaking discovery of human-induced pluripotent stem cells (iPSCs), many scientific reports have appeared on the differentiation of specialized cardiac cell types and derivation of patient-derived iPSCs for modeling cardiac disease or for potential therapeutic applications in regenerative medicine.

Despite these recent advances, significant hurdles need to be overcome before we are able to take full advantage of the benefits of patient-derived stem cells. How can we accomplish cardiovascular cell cultures and multicellular vascularized cardiac tissues with a similar level of maturation, organization, and function as observed in vivo – if possible or required at all? How can we mimic monogenic, polygenic, or multifactorial human cardiac diseases, or important aspects or phases of cardiac disease? Current advances in various technologies, including stem cell differentiation, genetic modification, tissue engineering or organoid formation, microfabrication, and microfluidics (organs-on-chip), which are needed to close the gap between human in vitro models and the patient, will be discussed in this Special Issue.

Prof. Dr. Robert Passier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cardiac disease modeling 
  • Organ-on-chip 
  • Organoids 
  • Tissue engineering 
  • Cardiac differentiation 
  • Human pluripotent stem cells 
  • Personalized medicine 
  • Regenerative medicine 
  • Assay development 
  • Drug testing/discovery

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 5114 KiB  
Article
Improved Atrial Differentiation of Human Pluripotent Stem Cells by Activation of Retinoic Acid Receptor Alpha (RARα)
by Verena Schwach, Carla Cofiño-Fabres, Simone A. ten Den and Robert Passier
J. Pers. Med. 2022, 12(4), 628; https://doi.org/10.3390/jpm12040628 - 13 Apr 2022
Cited by 5 | Viewed by 2226
Abstract
Human pluripotent stem cell (hPSC)-derived cardiomyocytes have proven valuable for modeling disease and as a drug screening platform. Here, we depict an optimized protocol for the directed differentiation of hPSCs toward cardiomyocytes with an atrial identity by modulating the retinoic acid signaling cascade [...] Read more.
Human pluripotent stem cell (hPSC)-derived cardiomyocytes have proven valuable for modeling disease and as a drug screening platform. Here, we depict an optimized protocol for the directed differentiation of hPSCs toward cardiomyocytes with an atrial identity by modulating the retinoic acid signaling cascade in spin embryoid bodies. The crucial steps of the protocol, including hPSC maintenance, embryoid body (EB) differentiation, the induction of cardiac mesoderm, direction toward the atrial phenotype, as well as molecular and functional characterization of the cardiomyocytes, are described. Atrial cardiomyocytes (AMs) can be generated within 14 days. Most importantly, we show that induction of the specific retinoic acid receptor alpha (RARα) increased the efficiency of atrial differentiation to 72% compared with 45% after modulating the retinoic acid (RA) pathway with all-trans RA (atRA). In contrast, the induction of RARβ signaling only had a minor impact on the efficiency of atrial differentiation (from about 45% to 50%). Similarly, the total yield of AM per EB of 5000 hPSCs was increased from 10,350 (2.07 per hPSC) to 16,120 (3.22 per hPSC) while selectively modulating RARα signaling. For further purification of the AMs, we describe a metabolic selection procedure that enhanced the AM percentage to more than 90% without compromising the AM yield (15,542 per EB, equal to 3.11 per hPSC) or functionality of the AMs as evaluated by RNAseq, immunostaining, and optical action potential measurement. Cardiomyocytes with distinct atrial and ventricular properties can be applied for selective pharmacology, such as the development of novel atrial-specific anti-arrhythmic agents, and disease modeling, including atrial fibrillation, which is the most common heart rhythm disorder. Moreover, fully characterized and defined cardiac subtype populations are of the utmost importance for potential cell-based therapeutic approaches. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells for Cardiac Differentiation and Disease Modeling)
►▼ Show Figures

Figure 1

16 pages, 6459 KiB  
Article
A New Versatile Platform for Assessment of Improved Cardiac Performance in Human-Engineered Heart Tissues
by Marcelo C. Ribeiro, José M. Rivera-Arbeláez, Carla Cofiño-Fabres, Verena Schwach, Rolf H. Slaats, Simone A. ten Den, Kim Vermeul, Albert van den Berg, José M Pérez-Pomares, Loes I. Segerink, Juan A. Guadix and Robert Passier
J. Pers. Med. 2022, 12(2), 214; https://doi.org/10.3390/jpm12020214 - 04 Feb 2022
Cited by 10 | Viewed by 4251
Abstract
Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) hold a great potential as human in vitro models for studying heart disease and for drug safety screening. Nevertheless, their associated immaturity relative to the adult myocardium limits their utility in cardiac research. In this [...] Read more.
Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) hold a great potential as human in vitro models for studying heart disease and for drug safety screening. Nevertheless, their associated immaturity relative to the adult myocardium limits their utility in cardiac research. In this study, we describe the development of a platform for generating three-dimensional engineered heart tissues (EHTs) from hPSC-CMs for the measurement of force while under mechanical and electrical stimulation. The modular and versatile EHT platform presented here allows for the formation of three tissues per well in a 12-well plate format, resulting in 36 tissues per plate. We compared the functional performance of EHTs and their histology in three different media and demonstrated that tissues cultured and maintained in maturation medium, containing triiodothyronine (T3), dexamethasone, and insulin-like growth factor-1 (TDI), resulted in a higher force of contraction, sarcomeric organization and alignment, and a higher and lower inotropic response to isoproterenol and nifedipine, respectively. Moreover, in this study, we highlight the importance of integrating a serum-free maturation medium in the EHT platform, making it a suitable tool for cardiovascular research, disease modeling, and preclinical drug testing. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells for Cardiac Differentiation and Disease Modeling)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

14 pages, 963 KiB  
Review
iPSCs and Exosomes: Partners in Crime Fighting Cardiovascular Diseases
by Giulia Germena and Rabea Hinkel
J. Pers. Med. 2021, 11(6), 529; https://doi.org/10.3390/jpm11060529 - 09 Jun 2021
Cited by 8 | Viewed by 2638
Abstract
Cardiovascular diseases are the leading cause of mortality worldwide. Understanding the mechanisms at the basis of these diseases is necessary in order to generate therapeutic approaches. Recently, cardiac tissue engineering and induced pluripotent stem cell (iPSC) reprogramming has led to a skyrocketing number [...] Read more.
Cardiovascular diseases are the leading cause of mortality worldwide. Understanding the mechanisms at the basis of these diseases is necessary in order to generate therapeutic approaches. Recently, cardiac tissue engineering and induced pluripotent stem cell (iPSC) reprogramming has led to a skyrocketing number of publications describing cardiovascular regeneration as a promising option for cardiovascular disease treatment. Generation of artificial tissue and organoids derived from induced pluripotent stem cells is in the pipeline for regenerative medicine. The present review summarizes the multiple approaches of heart regeneration with a special focus on iPSC application. In particular, we describe the strength of iPSCs as a tool to study the molecular mechanisms driving cardiovascular pathologies, as well as their potential in drug discovery. Moreover, we will describe some insights into novel discoveries of how stem-cell-secreted biomolecules, such as exosomes, could affect cardiac regeneration, and how the fine tuning of the immune system could be a revolutionary tool in the modulation of heart regeneration. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells for Cardiac Differentiation and Disease Modeling)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop