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Search Results (3)

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Keywords = c-kit+ cardiac stromal cells

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13 pages, 3279 KB  
Article
Single-Cell RNA Sequencing Reveals Distinct Cardiac-Derived Stromal Cell Subpopulations
by Jessica R. Hoffman, Arun R. Jayaraman, Sruti Bheri and Michael E. Davis
J. Cardiovasc. Dev. Dis. 2022, 9(11), 374; https://doi.org/10.3390/jcdd9110374 - 1 Nov 2022
Cited by 1 | Viewed by 4020
Abstract
Human cardiac-derived c-kit+ stromal cells (CSCs) have demonstrated efficacy in preclinical trials for the treatment of heart failure and myocardial dysfunction. Unfortunately, large variability in patient outcomes and cell populations remains a problem. Previous research has demonstrated that the reparative capacity of CSCs [...] Read more.
Human cardiac-derived c-kit+ stromal cells (CSCs) have demonstrated efficacy in preclinical trials for the treatment of heart failure and myocardial dysfunction. Unfortunately, large variability in patient outcomes and cell populations remains a problem. Previous research has demonstrated that the reparative capacity of CSCs may be linked to the age of the cells: CSCs derived from neonate patients increase cardiac function and reduce fibrosis. However, age-dependent differences between CSC populations have primarily been explored with bulk sequencing methods. In this work, we hypothesized that differences in CSC populations and subsequent cell therapy outcomes may arise from differing cell subtypes within donor CSC samples. We performed single-cell RNA sequencing on four neonatal CSC (nCSC) and five child CSC (cCSC) samples. Subcluster analysis revealed cCSC-enriched clusters upregulated in several fibrosis- and immune response-related genes. Module-based analysis identified upregulation of chemotaxis and ribosomal activity-related genes in nCSCs and upregulation of immune response and fiber synthesis genes in cCSCs. Further, we identified versican and integrin alpha 2 as potential markers for a fibrotic cell subtype. By investigating differences in patient-derived CSC populations at the single-cell level, this research aims to identify and characterize CSC subtypes to better optimize CSC-based therapy and improve patient outcomes. Full article
(This article belongs to the Special Issue Models and Methods for Computational Cardiology)
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20 pages, 5349 KB  
Article
Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction
by Konstantin V. Dergilev, Evgeny K. Shevchenko, Zoya I. Tsokolaeva, Irina B. Beloglazova, Ekaterina S. Zubkova, Maria A. Boldyreva, Mikhail Yu. Menshikov, Elizaveta I. Ratner, Dmitry Penkov and Yelena V. Parfyonova
Int. J. Mol. Sci. 2020, 21(24), 9603; https://doi.org/10.3390/ijms21249603 - 16 Dec 2020
Cited by 16 | Viewed by 3057
Abstract
Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived [...] Read more.
Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function. Full article
(This article belongs to the Special Issue Potential Application of Cell Sheets, for Tissue Engineering and Repairing Tissue)
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15 pages, 3851 KB  
Review
The Telocytes in the Subepicardial Niche
by Cristian Bogdan Iancu, Mugurel Constantin Rusu, Laurenţiu Mogoantă, Sorin Hostiuc and Oana Daniela Toader
Appl. Sci. 2019, 9(8), 1615; https://doi.org/10.3390/app9081615 - 18 Apr 2019
Cited by 11 | Viewed by 4044
Abstract
A great interest has developed over the last several years in research on interstitial Cajal-like cells (ICLCs), later renamed to telocytes (TCs). Such studies are restricted by diverse limitations. We aimed to critically review (sub)epicardial ICLCs/TCs and to bring forward supplemental immunohistochemical evidence [...] Read more.
A great interest has developed over the last several years in research on interstitial Cajal-like cells (ICLCs), later renamed to telocytes (TCs). Such studies are restricted by diverse limitations. We aimed to critically review (sub)epicardial ICLCs/TCs and to bring forward supplemental immunohistochemical evidence on (sub)epicardial stromal niche inhabitants. We tested the epicardial expressions of CD117/c-kit, CD34, Cytokeratin 7 (CK7), Ki67, Platelet-Derived Growth Factor Receptor (PDGFR)-α and D2-40 in adult human cardiac samples. The mesothelial epicardial cells expressed D2-40, CK7, CD117/c-kit and PDGFR-α. Subepicardial D2-40-positive lymphatic vessels and isolated D2-40-positive and CK7-positive subepicardial cells were also found. Immediate submesothelial spindle-shaped cells expressed Ki-67. Submesothelial stromal cells and endothelial tubes were PDGFR-α-positive and CD34-positive. The expression of CD34 was pan-stromal, so a particular stromal cell type could not be distinguished. The stromal expression of CD117/c-kit was also noted. It seems that epicardial TCs could not be regarded as belonging to a unique cell type until (pre)lymphatic endothelial cells are inadequately excluded. Markers such as CD117/c-kit or CD34 seem to be improper for identifying TCs as a distinctive cell type. Care should be taken when using the immunohistochemical method and histological interpretations, as they may not produce accurate results. Full article
(This article belongs to the Special Issue Immunohistochemical Expression)
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