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Biology
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Stem Cells for Cardiovascular Biology and Medicine
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Stem Cells for Cardiovascular Biology and Medicine

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 26815

Special Issue Editors

Dr. Nanako Kawaguchi

E-Mail Website
Guest Editor
Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
Interests: stem cells; chemokines; macrophagse; CXCR4; SDF-1; iPS cells
Special Issues, Collections and Topics in MDPI journals
Dr. Toshio Nakanishi

E-Mail Website
Co-Guest Editor
Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
Interests: stem cell; regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Various somatic stem cells, such as cardiac stem/progenitor cells (CSCs/CPCs), have been established and studied for future use in medical fields such as regenerative medicine. Induced pluripotent stem (iPS) cells have been studied for this purpose. Using iPS-cell-derived cardiac myocytes, an in vitro disease model was established for the evaluation of the effect of treatment with drugs and chemicals. Furthermore, the environments that stem cells inhabit, such as niches, are also important as they affect the behavior of stem cells. Chemokines (e.g., SDF-1) are associated with the migration and/or proliferation of stem cells and immune cell progenitors in bone marrow. However, controversies remain in stem cell research. For example, studies have shown both the existence and non-existence of CSCs/CPCs. The variation of in vitro differentiation is the strength of iPS cells, but the reported degree of variation varies across different studies.

This Special Issue focuses on current investigations of various somatic stem cells, including bone marrow (stem) cells, CSCs/CPCs, and iPS cells, and the environmental regulation of stem cells including chemokines. We are also interested in discussing how much we have currently achieved in these fields and what may be the obstacles to the further study of stem cells in cardiovascular biology and medicine. In this context, we welcome the submission of original research, short communication, and review manuscripts.

Dr. Nanako Kawaguchi
Dr. Toshio Nakanishi
Guest Editors

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. Biology 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 2700 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 stem cells
  • cardiac progenitor cells
  • iPS
  • cardiac development
  • cardiac differentiation
  • in vitro disease models
  • chemokines
  • CXCR4
  • SDF-1

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Published Papers (6 papers)

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Research

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16 pages, 4025 KiB  
Article
Quantitative Analysis of Factors Regulating Angiogenesis for Stem Cell Therapy
by Takahiro Shimazaki, Nobuhiro Noro, Kazuhiro Hagikura, Taro Matsumoto and Chikako Yoshida-Noro
Biology 2021, 10(11), 1212; https://doi.org/10.3390/biology10111212 - 20 Nov 2021
Cited by 7 | Viewed by 3621
Abstract
(1) Background: The control of angiogenesis is essential in disease treatment. We investigated angiogenesis-promoting or -suppressing factors and their molecular mechanisms. (2) Methods: Angiogenesis from HUVECs was quantitatively analyzed using the Angiogenesis Analysis Kit (Kurabo, Osaka, Japan). Human rAng-1-producing 107-35 CHO cells or [...] Read more.
(1) Background: The control of angiogenesis is essential in disease treatment. We investigated angiogenesis-promoting or -suppressing factors and their molecular mechanisms. (2) Methods: Angiogenesis from HUVECs was quantitatively analyzed using the Angiogenesis Analysis Kit (Kurabo, Osaka, Japan). Human rAng-1-producing 107-35 CHO cells or mouse DFAT-D1 cells were co-cultured with HUVEC. Antioxidant polyphenols were added to the culture. Gene expression was analyzed by RT-PCR. (3) Results: The addition of rAng-1-producing cells, their culture supernatant, or commercially available rAng-1 showed a promoting effect on angiogenesis. The co-culture of DFAT-D1 cells promoted angiogenesis. Polyphenols showed a dose-dependent inhibitory effect on angiogenesis. Luteolin and quercetin showed remarkable anti-angiogenic effects. The expression of vWF, Flk1, and PECAM-1 was increased by adding rAng-1-producing cell culture supernatant. Polyphenols suppressed these genes. Apigenin and luteolin markedly suppressed α-SMA and Flk1. Resveratrol and quercetin enhanced the expression of PPARγ, and luteolin suppressed the expression of COX-1. The expression of endothelial nitric oxide synthase (eNOS), an oxidative stress-related gene, was slightly increased by luteolin. These results suggest that polyphenols induce ROS reduction. (4) Conclusions: We showed the promoting effect of Ang-1 or DFAT and the suppressing effect of polyphenols on angiogenesis and studied their molecular mechanisms. These results help control angiogenesis in regenerative therapy. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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20 pages, 3963 KiB  
Article
Induced Pluripotent Stem Cell-Derived Cardiomyocytes with SCN5A R1623Q Mutation Associated with Severe Long QT Syndrome in Fetuses and Neonates Recapitulates Pathophysiological Phenotypes
by Emiko Hayama, Yoshiyuki Furutani, Nanako Kawaguchi, Akiko Seki, Yoji Nagashima, Keisuke Okita, Daiji Takeuchi, Rumiko Matsuoka, Kei Inai, Nobuhisa Hagiwara and Toshio Nakanishi
Biology 2021, 10(10), 1062; https://doi.org/10.3390/biology10101062 - 18 Oct 2021
Cited by 8 | Viewed by 3691
Abstract
The SCN5A R1623Q mutation is one of the most common genetic variants associated with severe congenital long QT syndrome 3 (LQT3) in fetal and neonatal patients. To investigate the properties of the R1623Q mutation, we established an induced pluripotent stem cell (iPSC) cardiomyocyte [...] Read more.
The SCN5A R1623Q mutation is one of the most common genetic variants associated with severe congenital long QT syndrome 3 (LQT3) in fetal and neonatal patients. To investigate the properties of the R1623Q mutation, we established an induced pluripotent stem cell (iPSC) cardiomyocyte (CM) model from a patient with LQTS harboring a heterozygous R1623Q mutation. The properties and pharmacological responses of iPSC-CMs were characterized using a multi-electrode array system. The biophysical characteristic analysis revealed that R1623Q increased open probability and persistent currents of sodium channel, indicating a gain-of-function mutation. In the pharmacological study, mexiletine shortened FPDcF in R1623Q-iPSC-CMs, which exhibited prolonged field potential duration corrected by Fridericia’s formula (FPDcF, analogous to QTcF). Meanwhile, E4031, a specific inhibitor of human ether-a-go-go-related gene (hERG) channel, significantly increased the frequency of arrhythmia-like early after depolarization (EAD) events. These characteristics partly reflect the patient phenotypes. To further analyze the effect of neonatal isoform, which is predominantly expressed in the fetal period, on the R1623Q mutant properties, we transfected adult form and neonatal isoform SCN5A of control and R1623Q mutant SCN5A genes to 293T cells. Whole-cell automated patch-clamp recordings revealed that R1623Q increased persistent Na+ currents, indicating a gain-of-function mutation. Our findings demonstrate the utility of LQT3-associated R1623Q mutation-harboring iPSC-CMs for assessing pharmacological responses to therapeutic drugs and improving treatment efficacy. Furthermore, developmental switching of neonatal/adult Nav1.5 isoforms may be involved in the pathological mechanisms underlying severe long QT syndrome in fetuses and neonates. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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16 pages, 3005 KiB  
Article
Human Blood Serum Induces p38-MAPK- and Hsp27-Dependent Migration Dynamics of Adult Human Cardiac Stem Cells: Single-Cell Analysis via a Microfluidic-Based Cultivation Platform
by Anna L. Höving, Julian Schmitz, Kazuko E. Schmidt, Johannes F. W. Greiner, Cornelius Knabbe, Barbara Kaltschmidt, Alexander Grünberger and Christian Kaltschmidt
Biology 2021, 10(8), 708; https://doi.org/10.3390/biology10080708 - 24 Jul 2021
Cited by 18 | Viewed by 3743
Abstract
Migratory capabilities of adult human stem cells are vital for assuring endogenous tissue regeneration and stem cell-based clinical applications. Although human blood serum has been shown to be beneficial for cell migration and proliferation, little is known about its impact on the migratory [...] Read more.
Migratory capabilities of adult human stem cells are vital for assuring endogenous tissue regeneration and stem cell-based clinical applications. Although human blood serum has been shown to be beneficial for cell migration and proliferation, little is known about its impact on the migratory behavior of cardiac stem cells and underlying signaling pathways. Within this study, we investigated the effects of human blood serum on primary human cardiac stem cells (hCSCs) from the adult heart auricle. On a technical level, we took advantage of a microfluidic cultivation platform, which allowed us to characterize cell morphologies and track migration of single hCSCs via live cell imaging over a period of up to 48 h. Our findings showed a significantly increased migration distance and speed of hCSCs after treatment with human serum compared to control. Exposure of blood serum-stimulated hCSCs to the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB239063 resulted in significantly decreased migration. Moreover, we revealed increased phosphorylation of heat shock protein 27 (Hsp27) upon serum treatment, which was diminished by p38-MAPK-inhibition. In summary, we demonstrate human blood serum as a strong inducer of adult human cardiac stem cell migration dependent on p38-MAPK/Hsp27-signalling. Our findings further emphasize the great potential of microfluidic cultivation devices for assessing spatio-temporal migration dynamics of adult human stem cells on a single-cell level. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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27 pages, 12567 KiB  
Article
Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model
by Pau Urdeitx and Mohamed H. Doweidar
Biology 2021, 10(2), 135; https://doi.org/10.3390/biology10020135 - 9 Feb 2021
Cited by 8 | Viewed by 3580
Abstract
Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In [...] Read more.
Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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Review

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14 pages, 893 KiB  
Review
Stem Cell Studies in Cardiovascular Biology and Medicine: A Possible Key Role of Macrophages
by Nanako Kawaguchi and Toshio Nakanishi
Biology 2022, 11(1), 122; https://doi.org/10.3390/biology11010122 - 12 Jan 2022
Cited by 8 | Viewed by 4632
Abstract
Stem cells are used in cardiovascular biology and biomedicine, and research in this field is expanding. Two types of stem cells have been used in research: induced pluripotent and somatic stem cells. Stem cell research in cardiovascular medicine has developed rapidly following the [...] Read more.
Stem cells are used in cardiovascular biology and biomedicine, and research in this field is expanding. Two types of stem cells have been used in research: induced pluripotent and somatic stem cells. Stem cell research in cardiovascular medicine has developed rapidly following the discovery of different types of stem cells. Induced pluripotent stem cells (iPSCs) possess potent differentiation ability, unlike somatic stem cells, and have been postulated for a long time. However, differentiating into adult-type mature and functional cardiac myocytes (CMs) remains difficult. Bone marrow stem/stromal cells (BMSCs), adipose-derived stem cells (ASCs), and cardiac stem cells (CSCs) are somatic stem cells used for cardiac regeneration. Among somatic stem cells, bone marrow stem/stromal cells (BMSCs) were the first to be discovered and are relatively well-characterized. BMSCs were once thought to have differentiation ability in infarcted areas of the heart, but it has been identified that paracrine cytokines and micro-RNAs derived from BMSCs contributed to that effect. Moreover, vesicles and exosomes from these cells have similar effects and are effective in cardiac repair. The molecular signature of exosomes can also be used for diagnostics because exosomes have the characteristics of their origin cells. Cardiac stem cells (CSCs) differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells, and supply cardiomyocytes during myocardial infarction by differentiating into newly formed cardiomyocytes. Stem cell niches and inflammatory cells play important roles in stem cell regulation and the recovery of damaged tissues. In particular, chemokines can contribute to the communication between inflammatory cells and stem cells. In this review, we present the current status of this exciting and promising research field. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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Figure 1

21 pages, 1320 KiB  
Review
Disease Modeling of Mitochondrial Cardiomyopathy Using Patient-Specific Induced Pluripotent Stem Cells
by Takeshi Tokuyama, Razan Elfadil Ahmed, Nawin Chanthra, Tatsuya Anzai and Hideki Uosaki
Biology 2021, 10(10), 981; https://doi.org/10.3390/biology10100981 - 29 Sep 2021
Cited by 4 | Viewed by 6338
Abstract
Mitochondrial cardiomyopathy (MCM) is characterized as an oxidative phosphorylation disorder of the heart. More than 100 genetic variants in nuclear or mitochondrial DNA have been associated with MCM. However, the underlying molecular mechanisms linking genetic variants to MCM are not fully understood due [...] Read more.
Mitochondrial cardiomyopathy (MCM) is characterized as an oxidative phosphorylation disorder of the heart. More than 100 genetic variants in nuclear or mitochondrial DNA have been associated with MCM. However, the underlying molecular mechanisms linking genetic variants to MCM are not fully understood due to the lack of appropriate cellular and animal models. Patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) provide an attractive experimental platform for modeling cardiovascular diseases and predicting drug efficacy to such diseases. Here we introduce the pathological and therapeutic studies of MCM using iPSC-CMs and discuss the questions and latest strategies for research using iPSC-CMs. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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