Characterisation of endogenous cardiac stem cells (eCSCs) isolated from the four chambers of the adult human heart

In contrast with some adult human organs, such as liver or skin, the adult human heart shows very limited self-regeneration capacity, attributed to the negligible presence of resident cardiac stem cells or cardiac progenitors [...]

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Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells

Cells ◽

10.3390/cells9061472 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1472 ◽

Cited By ~ 1

Author(s):

Anna L. Höving ◽

Kazuko E. Schmidt ◽

Madlen Merten ◽

Jassin Hamidi ◽

Ann-Katrin Rott ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

P38 Mapk ◽

Regulatory Networks ◽

Human Blood Plasma ◽

Cardiac Stem Cells ◽

Dependent Manner ◽

Protective Effects ◽

Adult Human ◽

Age And Sex

During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells.

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There is a clear distribution pattern of viable resident c-kit positive cardiac stem cells in the human heart in patients suffering from ischemic cardiomyopathy

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0029-1246864 ◽

2010 ◽

Vol 58 (S 01) ◽

Author(s):

J Garbade ◽

M Arsalan ◽

F Woitek ◽

M Barten ◽

V Adams ◽

...

Keyword(s):

Stem Cells ◽

Distribution Pattern ◽

Ischemic Cardiomyopathy ◽

Human Heart ◽

Cardiac Stem Cells

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β1 - and β2 -adrenoceptor responses in cardiomyocytes derived from human embryonic stem cells: comparison with failing and non-failing adult human heart

British Journal of Pharmacology ◽

10.1038/sj.bjp.0707619 ◽

2008 ◽

Vol 153 (4) ◽

pp. 751-759 ◽

Cited By ~ 52

Author(s):

M Brito-Martins ◽

S E Harding ◽

N N Ali

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Human Heart ◽

Embryonic Stem ◽

Adult Human

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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

Biology ◽

10.3390/biology10080708 ◽

2021 ◽

Vol 10 (8) ◽

pp. 708

Author(s):

Anna L. Höving ◽

Julian Schmitz ◽

Kazuko E. Schmidt ◽

Johannes F. W. Greiner ◽

Cornelius Knabbe ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Blood Serum ◽

P38 Mapk ◽

Human Blood ◽

Human Blood Serum ◽

Cardiac Stem Cells ◽

Human Stem Cells ◽

Adult Human ◽

Migration Dynamics

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.

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The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells

Nature Clinical Practice Cardiovascular Medicine ◽

10.1038/ncpcardio0771 ◽

2007 ◽

Vol 4 (S1) ◽

pp. S27-S39 ◽

Cited By ~ 96

Author(s):

Harald C Ott ◽

Thomas S Matthiesen ◽

Johannes Brechtken ◽

Suzanne Grindle ◽

Saik-Kia Goh ◽

...

Keyword(s):

Stem Cells ◽

Progenitor Cells ◽

Human Heart ◽

Adult Human

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Abstract 352: The Effect of the Extracellular Matrix of Failing Hearts on Cardiac Stem Cells

Circulation Research ◽

10.1161/res.119.suppl_1.352 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Dawn A Delfín ◽

Joshua DeAguero ◽

Elizabeth N McKown

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Stem Cell ◽

Human Heart ◽

Therapeutic Option ◽

Cardiac Stem Cells ◽

Matricellular Proteins ◽

Adrenergic Stimulation ◽

Failing Heart ◽

Cells Cultured

Objective: Stem cell therapy to repair cardiac damage, caused by the pathological remodeling that occurs in cardiovascular disease, represents a cutting edge therapeutic option toward preventing and treating heart failure. There is a paucity of information on how the phenotypes of stem cells are altered in the “hostile” environment of pathologically remodeled hearts. The objective of this study was to (a) determine the phenotypes of cardiac stem cells cultured on failing versus normal human heart tissue, and (b) to characterize pathology of failing human heart samples. Methods: We isolated the extracellular matrix (ECM) from end-stage failing human hearts (compared to control human hearts) and used the isolated ECM to coat tissue culture plates. The ECM represents the scaffold of the heart in which stem cells will integrate, proliferate, and differentiate. We then cultured induced pluripotent stem cell-derived cardiac progenitor cells on the cardiac-ECM plates and analyzed their phenotypes (morphology, differentiation into cardiomyocytes, and gene expression). We also performed analysis of the failing cardiac tissue itself to determine the extent of fibrosis and expression of various ECM and matricellular proteins. Results: Cells cultured on failing heart ECM showed important differences compared to those on control heart ECM, including reduced cell-matrix adhesion and altered responses to beta-adrenergic stimulation. The failing heart shows increased fibrosis and differential expression of specific ECM and matricellular proteins. Significance: We will use these data to determine how best to direct cardiac stem cells used for tissue generation in severely damaged hearts toward differentiation into functioning cardiomyocytes.

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