Human Cardiac Mesenchymal Stromal Cells From Right and Left Ventricles Display Differences in Number, Function, and Transcriptomic Profile

Abstract

Background: Left ventricle (LV) and right ventricle (RV) are characterized by wellknown 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.

Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy

“…Typical events envisage the differentiation of fibroblast into myofibroblast leading to extracellular matrix (ECM) deposition. Different cells can be considered myofibroblast precursors, among which resident cardiac fibroblasts [ 7 , 8 , 9 ] and cardiac mesenchymal stromal cells (C-MSC) [ 10 , 11 ] can be mentioned. In this context, the typical pro-fibrotic factor transforming growth factor-β (TGF-β) can promote fibrotic remodeling [ 12 , 13 ].…”

Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy

“…Thus, CSCs appear to contribute to cardiac healing after ischemic injury and lead to improved heart function when tested in animal models of post-ischemic HF. They can undergo adipogenic differentiation in the heart in some pathological conditions such as obesity [21] and arrhythmogenic cardiomyopathy (ACM) [22,23] . In particular, in ACM, the mesenchymal component of CSCs is believed to be the source of cardiac adipocytes [22,23] .…”

“…They can undergo adipogenic differentiation in the heart in some pathological conditions such as obesity [21] and arrhythmogenic cardiomyopathy (ACM) [22,23] . In particular, in ACM, the mesenchymal component of CSCs is believed to be the source of cardiac adipocytes [22,23] . Human-derived CSCs have recently been shown to express the ACE2 receptor and are susceptible to SARS-CoV-2 infection [24] .…”

Role of Podoplanin-Positive Cells in Cardiac Fibrosis and Angiogenesis After Ischemia

“…Like MSCs, mesenchymal stromal cells have also been identified in the heart and specifically in both ventricles (Stadiotti et al, 2020). Histological analysis showed a greater percentage of stromal cells in the right ventricle versus the left one; cardiac mesenchymal stromal cells from the right ventricle show the same surface markers as the cells isolated from the left ventricle (Stadiotti et al, 2020).…”

“…Like MSCs, mesenchymal stromal cells have also been identified in the heart and specifically in both ventricles (Stadiotti et al, 2020). Histological analysis showed a greater percentage of stromal cells in the right ventricle versus the left one; cardiac mesenchymal stromal cells from the right ventricle show the same surface markers as the cells isolated from the left ventricle (Stadiotti et al, 2020). There is a very thin line that separates MSCs from mesenchymal stromal cells, and in the heart, a dynamic flux of cardiac stromal cells has been described, which is much that like when MSCs express PDGFRα (Farbehi et al, 2019).…”