Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Isolation and Cultivation of Adult Human Cardiac Stem Cells from Heart Auricles
2.2. Immunohistochemistry and Immunocytochemistry
2.3. Flow Cytometry
2.4. Cardiac Differentiation of hCSCs
2.5. Blood Plasma
2.6. p38-MAPK Inhibition
2.7. Proliferation Assay
2.8. Orangu Cell Viability Assay
2.9. Senescence-Associated β-Galactosidase Assay
2.10. RNA Isolation and Sequencing
2.11. ELISA
3. Results
3.1. Identification of Nestin+/S100B+ Cells in the Human Heart Auricle Tissue
3.2. Successfully iIsolated Putative Human Cardiac Stem Cells from Heart Auricle Tissue Show High Clonal Efficiency and Capability for Cardiosphere Formation
3.3. Isolated Cells Express Known Marker Proteins of Cardiac Stem and Progenitor Cells
3.4. HCSCs Are Able to Give Rise to Cardiomyocytes In Vitro
3.5. Blood Plasma and Blood Serum Strongly Enhance Proliferation-Inducing Effects of Blood Plasma on Adult Human Cardiac Stem Cells
3.6. Age and Sex of Blood Serum Donors Do Not Affect Beneficial Effects on Proliferation and Metabolism of hCSCs
3.7. Exposure of hCSCs to Blood Serum from Young Female or Male Donors Results in Significantly Enhanced Protection against Senescence Compared to Serum from Old Female Individuals
3.8. Young Blood Serum Enhances Differential Global Gene Expression of hCSCs
3.9. Global Gene Expression Profiling Indicates Age-Dependent Clusters of Blood-Serum-Treated Adult Stem Cells
3.10. Gene Ontology (GO) Term Analysis Reveals Downregulation of Attachment-Associated Genes and Upregulation of Proliferation-Associated GO Terms, Including p38-MAPK
3.11. Beneficial Effects of Blood Plasma on Proliferation and Protection of hCSCs Against Senescence Are Partially Mediated by p38 MAPK-Signaling
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Höving, A.L.; Schmidt, K.E.; Merten, M.; Hamidi, J.; Rott, A.-K.; Faust, I.; Greiner, J.F.W.; Gummert, J.; Kaltschmidt, B.; Kaltschmidt, C.; et al. Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells. Cells 2020, 9, 1472. https://doi.org/10.3390/cells9061472
Höving AL, Schmidt KE, Merten M, Hamidi J, Rott A-K, Faust I, Greiner JFW, Gummert J, Kaltschmidt B, Kaltschmidt C, et al. Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells. Cells. 2020; 9(6):1472. https://doi.org/10.3390/cells9061472
Chicago/Turabian StyleHöving, Anna L., Kazuko E. Schmidt, Madlen Merten, Jassin Hamidi, Ann-Katrin Rott, Isabel Faust, Johannes F. W. Greiner, Jan Gummert, Barbara Kaltschmidt, Christian Kaltschmidt, and et al. 2020. "Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells" Cells 9, no. 6: 1472. https://doi.org/10.3390/cells9061472