New Perspectives to Repair a Broken Heart

Gaetani, Roberto; Barile, Lucio; Forte, Elvira; Chimenti, Isotta; Ionta, Vittoria; Consiglio, Alberto Di; Miraldi, Fabio; Frati, Giacomo; Messina, Elisa; Giacomello, Alessandro

doi:10.2174/187152509787847128

Cited by 27 publications

(17 citation statements)

References 148 publications

(112 reference statements)

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“…On the other hand, the SCAMI trial showed no improvement in function and size of cardiac chamber after MNC intracoronary infusion (381 × 10 6 cells, 6.1 days after revascularization) when evaluated by cardiac MRI [60], whereas others showed limited improvement of LVEF [14]. The long-term effect is not superior to traditional pharmacological therapies [12, 61] and there is also obvious change in cardiac remodelling [60]. The effect of cell therapy is more related to paracrine effects, which operate to salvage the cells after MI rather than induce new functional tissue in or around the infarct area.…”

Section: Myocardiac Restoration Methodologiesmentioning

confidence: 99%

Myocardial Restoration: Is It the Cell or the Architecture or Both?

Kofidis

2012

Cardiology Research and Practice

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Myocardial infarction is the leading cause of death in developed countries. Cardiac cell therapy has been introduced to clinical trials for more than ten years but its results are still controversial. Tissue engineering has addressed some limitations of cell therapy and appears to be a promising solution for cardiac regeneration. In this review, we would like to summarize the current understanding about the therapeutic effect of cell therapy and tissue engineering under purview of functional and structural aspects, highlighting actual roles of each therapy towards clinical application.

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Section: Myocardiac Restoration Methodologiesmentioning

confidence: 99%

Myocardial Restoration: Is It the Cell or the Architecture or Both?

Kofidis

2012

Cardiology Research and Practice

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“…The vast majority of clinically relevant cardiovascular disease results from the death of cardiac cells that are replaced by noncontractile fibrotic tissue, thus leading to pathological ventricular remodeling and heart failure [1,2]. Therefore, an intense effort during the last decade has been focused on identifying endogenous cardiac progenitor cells (CPCs) that can be expanded ex vivo and reintroduced as an autologous regenerative therapy [3,4]. A promising candidate population of resident CPCs can be readily obtained from cells that spontaneously migrate out of primary cardiac explants (explant-derived cells [EDCs]) and form cardiospheres (CSps) which recreate in vitro a niche-like microtissue [5].…”

Section: Introductionmentioning

confidence: 99%

TGFβ-Dependent Epithelial-to-Mesenchymal Transition Is Required to Generate Cardiospheres from Human Adult Heart Biopsies

Forte

Miraldi

Chimenti³

et al. 2012

Stem Cells and Development

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Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor b1 (TGFb1) and drastically blocked by the type I TGFb-receptor inhibitor SB431452, indicating that TGFb-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFb is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.

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“…Human CPCs can be isolated with clinically compliant protocols [6] and have been tested in few clinical trials as a promising tool for cardiac regenerative medicine [7, 8]. Unfortunately, despite the positive preclinical results [9, 10], regenerative medicine still cannot be considered a strong alternative to transplantation. It has been demonstrated that only 5–10% of the injected cells can be detected after 1 day from the procedure in the damaged myocardium, meaning that many cells are lost within few hours after injection [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment

Pagano

Angelini

Castaldo

et al. 2017

Stem Cells International

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Human resident cardiac progenitor cells (CPCs) isolated as cardiosphere-derived cells (CDCs) are under clinical evaluation as a therapeutic product for cardiac regenerative medicine. Unfortunately, limited engraftment and differentiation potential of transplanted cells significantly hamper therapeutic success. Moreover, maladaptive remodelling of the extracellular matrix (ECM) during heart failure progression provides impaired biological and mechanical signals to cardiac cells, including CPCs. In this study, we aimed at investigating the differential effect on the phenotype of human CDCs of cardiac fibroblast-derived ECM substrates from healthy or diseased hearts, named, respectively, normal or pathological cardiogel (CG-N/P). After 7 days of culture, results show increased levels of cardiogenic gene expression (NKX2.5, CX43) on both decellularized cardiogels compared to control, while the proportion and staining patterns of GATA4, OCT4, NKX2.5, ACTA1, VIM, and CD90-positive CPCs were not affected, as assessed by immunofluorescence microscopy and flow cytometry analyses. Nonetheless, CDCs cultured on CG-N secreted significantly higher levels of osteopontin, FGF6, FGF7, NT-3, IGFBP4, and TIMP-2 compared to those cultured on CG-P, suggesting overall a reduced trophic and antiremodelling paracrine profile of CDCs when in contact with ECM from pathological cardiac fibroblasts. These results provide novel insights into the bidirectional interplay between cardiac ECM and CPCs, potentially affecting CPC biology and regenerative potential.

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New Perspectives to Repair a Broken Heart

Cited by 27 publications

References 148 publications

Myocardial Restoration: Is It the Cell or the Architecture or Both?

Myocardial Restoration: Is It the Cell or the Architecture or Both?

TGFβ-Dependent Epithelial-to-Mesenchymal Transition Is Required to Generate Cardiospheres from Human Adult Heart Biopsies

Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment

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