TY - JOUR
T1 - Human Cardiac Mesenchymal Stromal Cells From Right and Left Ventricles Display Differences in Number, Function, and Transcriptomic Profile
AU - Stadiotti, Ilaria
AU - Piacentini, Luca
AU - Vavassori, Chiara
AU - Chiesa, Mattia
AU - Scopece, Alessandro
AU - Guarino, Anna
AU - Micheli, Barbara
AU - Polvani, Gianluca
AU - Colombo, Gualtiero Ivanoe
AU - Pompilio, Giulio
AU - Sommariva, Elena
N1 - Funding Information:
We are deeply grateful to heart donors? families, who consented the donation for both transplantation and research use. We also acknowledge the fundamental help of Dr. Paolo Poggio, Dr. Gianluca Perrucci, and Dr. Rosaria Santoro for data acquisition and analysis. Funding. The project was funded by Italian Ministry of Health (RC2019 EF5C ID: 2754330).
Publisher Copyright:
© Copyright © 2020 Stadiotti, Piacentini, Vavassori, Chiesa, Scopece, Guarino, Micheli, Polvani, Colombo, Pompilio and Sommariva.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/24
Y1 - 2020/6/24
N2 - Background: Left ventricle (LV) and right ventricle (RV) are characterized by well-known physiological differences, mainly related to their different embryological origin, hemodynamic environment, function, structure, and cellular composition. Nevertheless, scarce information is available about cellular peculiarities between left and right ventricular chambers in physiological and pathological contexts. Cardiac mesenchymal stromal cells (C-MSC) are key cells affecting many functions of the heart. Differential features that distinguish LV from RV C-MSC are still underappreciated. Aim: To analyze the physiological differential amount, function, and transcriptome of human C-MSC in LV versus (vs.) RV. Methods: Human cardiac specimens of LV and RV from healthy donors were used for tissue analysis of C-MSC number, and for C-MSC isolation. Paired LV and RV C-MSC were compared as for surface marker expression, cell proliferation/death ratio, migration, differentiation capabilities, and transcriptome profile. Results: Histological analysis showed a greater percentage of C-MSC in RV vs. LV tissue. Moreover, a higher C-MSC amount was obtained from RV than from LV after isolation procedures. LV and RV C-MSC are characterized by a similar proportion of surface markers. Functional studies revealed comparable cell growth curves in cells from both ventricles. Conversely, LV C-MSC displayed a higher apoptosis rate and RV C-MSC were characterized by a higher migration speed and collagen deposition. Consistently, transcriptome analysis showed that genes related to apoptosis regulation or extracellular matrix organization and integrins were over-expressed in LV and RV, respectively. Besides, we revealed additional pathways specifically associated with LV or RV C-MSC, including energy metabolism, inflammatory response, cardiac conduction, and pluripotency. Conclusion: Taken together, these results contribute to the functional characterization of RV and LV C-MSC in physiological conditions. This information suggests a possible differential role of the stromal compartment in chamber-specific pathologic scenarios.
AB - Background: Left ventricle (LV) and right ventricle (RV) are characterized by well-known physiological differences, mainly related to their different embryological origin, hemodynamic environment, function, structure, and cellular composition. Nevertheless, scarce information is available about cellular peculiarities between left and right ventricular chambers in physiological and pathological contexts. Cardiac mesenchymal stromal cells (C-MSC) are key cells affecting many functions of the heart. Differential features that distinguish LV from RV C-MSC are still underappreciated. Aim: To analyze the physiological differential amount, function, and transcriptome of human C-MSC in LV versus (vs.) RV. Methods: Human cardiac specimens of LV and RV from healthy donors were used for tissue analysis of C-MSC number, and for C-MSC isolation. Paired LV and RV C-MSC were compared as for surface marker expression, cell proliferation/death ratio, migration, differentiation capabilities, and transcriptome profile. Results: Histological analysis showed a greater percentage of C-MSC in RV vs. LV tissue. Moreover, a higher C-MSC amount was obtained from RV than from LV after isolation procedures. LV and RV C-MSC are characterized by a similar proportion of surface markers. Functional studies revealed comparable cell growth curves in cells from both ventricles. Conversely, LV C-MSC displayed a higher apoptosis rate and RV C-MSC were characterized by a higher migration speed and collagen deposition. Consistently, transcriptome analysis showed that genes related to apoptosis regulation or extracellular matrix organization and integrins were over-expressed in LV and RV, respectively. Besides, we revealed additional pathways specifically associated with LV or RV C-MSC, including energy metabolism, inflammatory response, cardiac conduction, and pluripotency. Conclusion: Taken together, these results contribute to the functional characterization of RV and LV C-MSC in physiological conditions. This information suggests a possible differential role of the stromal compartment in chamber-specific pathologic scenarios.
KW - cardiac mesenchymal stromal cells
KW - cardiac ventricles
KW - functional studies
KW - left ventricle
KW - right ventricle
KW - transcriptome
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UR - http://www.scopus.com/inward/citedby.url?scp=85087708856&partnerID=8YFLogxK
U2 - 10.3389/fphys.2020.00604
DO - 10.3389/fphys.2020.00604
M3 - Article
AN - SCOPUS:85087708856
VL - 11
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 604
ER -