An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit+ cardiac progenitor cells' therapeutic potential

Cardiovascular diseases, such as ischemic heart disease, remain the most common cause of death worldwide. Regenerative medicine with stem cell therapy is a promising tool for cardiac repair. Combination of different cell types has been shown to improve the therapeutic potential, which is thought to be due to synergistic or complimentary reparative effects. We investigated if the combination of cardiac progenitor cells (CPCs) of right atrial appendage (RAA) and left ventricle (LV) that are isolated from the same patient exert synergistic or complimentary paracrine effects for apoptotic cell death and angiogenesis in an in vitro model. Flow cytometry analysis showed that both RAA and LV CPCs expressed the mesenchymal cell markers CD90 and CD105, and were predominantly negative for the hematopoietic cell marker, CD34. Analysis of conditioned media (CM) collected from the CPCs cultured either alone or in combination in serum-deprived hypoxic conditions to simulate ischemia showed marked increase in the level of pro-survival hepatocyte growth factor and pro-angiogenic vascular endothelial growth factor-A in the combined RAA and LV CPC group. Next, to determine the therapeutic potential of CM, AC16 human ventricular cardiomyocytes and human umbilical vein endothelial cells (HUVECs) were treated with CM. Results showed a significant reduction in hypoxia-induced apoptosis of human cardiomyocytes treated with CM collected from combined RAA and LV CPC group. Similarly, matrigel assay showed a significantly increased tube length formed by HUVECs when treated with CM from combined RAA and LV CPC group. Our study provided evidence that the combination of RAA CPCs and LV CPCs may have superior therapeutic effects due to synergistic paracrine effects for cardiac repair. Therefore, in vivo studies are warranted to determine if a combination of different stem cell types have greater therapeutic potential than single-cell therapies.

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Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization

Expert Opinion on Drug Metabolism & Toxicology ◽

10.1080/17425255.2021.1894122 ◽

2021 ◽

Author(s):

Sarah D. Burnett ◽

Alexander D. Blanchette ◽

Weihsueh A. Chiu ◽

Ivan Rusyn

Keyword(s):

Stem Cell ◽

Pluripotent Stem Cell ◽

In Vitro Model ◽

Induced Pluripotent Stem Cell ◽

Hazard Identification ◽

Risk Characterization ◽

Vitro Model ◽

Induced Pluripotent

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Human stem cell-derived cardiac spheroids as 3D in vitro model for cardiotoxicity testing

Journal of Pharmacological and Toxicological Methods ◽

10.1016/j.vascn.2020.106848 ◽

2020 ◽

Vol 105 ◽

pp. 106848

Author(s):

Ki-Suk Kim

Keyword(s):

Stem Cell ◽

In Vitro Model ◽

Human Stem Cell ◽

3D In Vitro Model ◽

Vitro Model

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Regulation and Directing Stem Cell Fate by Tissue Engineering Functional Microenvironments: Scaffold Physical and Chemical Cues

Stem Cells International ◽

10.1155/2019/2180925 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 8

Author(s):

Fei Xing ◽

Lang Li ◽

Changchun Zhou ◽

Cheng Long ◽

Lina Wu ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Stem Cell ◽

Growth Factors ◽

Cell Fate ◽

Chemical Cues ◽

Physical Factors ◽

Stem Cell Fate ◽

Physical And Chemical

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

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