Cardiac Progenitor Cells: The Matrix Has You

Castaldo, Clotilde; Chimenti, Isotta

doi:10.1002/sctm.18-0023

Cited by 10 publications

(7 citation statements)

References 53 publications

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“…Moreover, we noticed that measurements of regional wall motion parameters by speckle tracking analysis could reveal early changes in matrix remodeling upon CPC injection (17). The anti-fibrotic effects of CPCs seem to be paracrine in nature and seem to be mediated through exosomes, microRNAs, and endoglin (18, 19). The mechanisms of action are not fully understood however, mainly due to a lack of in vivo insights in matrix remodeling and the role of associated CF (20).…”

Section: Introductionmentioning

confidence: 99%

Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis

Gartner

Deddens

Mol

et al. 2019

Front. Cardiovasc. Med.

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Cardiac fibroblasts play a key role in chronic heart failure. The conversion from cardiac fibroblast to myofibroblast as a result of cardiac injury, will lead to excessive matrix deposition and a perpetuation of pro-fibrotic signaling. Cardiac cell therapy for chronic heart failure may be able to target fibroblast behavior in a paracrine fashion. However, no reliable human fibrotic tissue model exists to evaluate this potential effect of cardiac cell therapy. Using a gelatin methacryloyl hydrogel and human fetal cardiac fibroblasts (hfCF), we created a 3D in vitro model of human cardiac fibrosis. This model was used to study the possibility to modulate cellular fibrotic responses. Our approach demonstrated paracrine inhibitory effects of cardiac progenitor cells (CPC) on both cardiac fibroblast activation and collagen synthesis in vitro and revealed that continuous cross-talk between hfCF and CPC seems to be indispensable for the observed anti-fibrotic effect.

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Section: Introductionmentioning

confidence: 99%

Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis

Gartner

Deddens

Mol

et al. 2019

Front. Cardiovasc. Med.

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“…As mentioned previously, the microenvironment is also modulated by cellular diversity, including supporting cells, such as stromal primitive cells, pericytes, or fibroblasts (Figure 2; Castaldo and Chimenti, 2018;Forte et al, 2018). Several studies in 3D culture systems have shown the beneficial effects of fibroblasts co-culture on ESC-or iPSC-derived CM differentiation (Liau et al, 2011;Ou et al, 2011;Valls-Margarit et al, 2019).…”

Section: New Approaches In Modeling the Artificial Microenvironmentmentioning

confidence: 89%

Building an Artificial Cardiac Microenvironment: A Focus on the Extracellular Matrix

Pagliarosi

Picchio

Chimenti

et al. 2020

Front. Cell Dev. Biol.

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The increased knowledge in cell signals and stem cell differentiation, together with the development of new technologies, such as 3D bioprinting, has made the generation of artificial tissues more feasible for in vitro studies and in vivo applications. In the human body, cell fate, function, and survival are determined by the microenvironment, a rich and complex network composed of extracellular matrix (ECM), different cell types, and soluble factors. They all interconnect and communicate, receiving and sending signals, modulating and responding to cues. In the cardiovascular field, the culture of stem cells in vitro and their differentiation into cardiac phenotypes is well established, although differentiated cardiomyocytes often lack the functional maturation and structural organization typical of the adult myocardium. The recreation of an artificial microenvironment as similar as possible to the native tissue, though, has been shown to partly overcome these limitations, and can be obtained through the proper combination of ECM molecules, different cell types, bioavailability of growth factors (GFs), as well as appropriate mechanical and geometrical stimuli. This review will focus on the role of the ECM in the regulation of cardiac differentiation, will provide new insights on the role of supporting cells in the generation of 3D artificial tissues, and will also present a selection of the latest approaches to recreate a cardiac microenvironment in vitro through 3D bioprinting approaches.

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“…The hypothesis that stem cells could exert therapeutic activity through their secretions is highly plausible as stem cell secretions are known to include many biologically potent molecules such as growth factors, cytokines, chemokines, and bioactive lipids that could elicit wide-ranging physiological effects ( Postiglione et al, 2003 ; Anthony and Shiels, 2013 ). Growing evidence suggests that adult stem/progenitor cells may exert dramatic effects on the repair of various tissues through secreted factors including EVs ( Maguire, 2013 ; Castaldo and Chimenti, 2018 ). Indeed, up to 80% of the therapeutic activities of adult stem/progenitor cells injected in ischemic hearts have been shown to occur through paracrine mediated effects ( Chimenti et al, 2010 ), giving rise to the novel notion of stem cell therapy without cells ( Maguire, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Human Cardiac Progenitor Cell-Derived Extracellular Vesicles Exhibit Promising Potential for Supporting Cardiac Repair in Vitro

Romano¹,

Belviso²,

Sacco³

et al. 2022

Front. Physiol.

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Although human Cardiac Progenitor Cells (hCPCs) are not retained by host myocardium they still improve cardiac function when injected into ischemic heart. Emerging evidence supports the hypothesis that hCPC beneficial effects are induced by paracrine action on resident cells. Extracellular vesicles (EVs) are an intriguing mechanism of cell communication based on the transport and transfer of peptides, lipids, and nucleic acids that have the potential to modulate signaling pathways, cell growth, migration, and proliferation of recipient cells. We hypothesize that EVs are involved in the paracrine effects elicited by hCPCs and held accountable for the response of the infarcted myocardium to hCPC-based cell therapy. To test this theory, we collected EVs released by hCPCs isolated from healthy myocardium and evaluated the effects they elicited when administered to resident hCPC and cardiac fibroblasts (CFs) isolated from patients with post-ischemic end-stage heart failure. Evidence emerging from our study indicated that hCPC-derived EVs impacted upon proliferation and survival of hCPCs residing in the ischemic heart and regulated the synthesis and deposition of extracellular-matrix by CFs. These findings suggest that beneficial effects exerted by hCPC injection are, at least to some extent, ascribable to the delivery of signals conveyed by EVs.

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Cardiac Progenitor Cells: The Matrix Has You

Cited by 10 publications

References 53 publications

Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis

Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis

Building an Artificial Cardiac Microenvironment: A Focus on the Extracellular Matrix

Human Cardiac Progenitor Cell-Derived Extracellular Vesicles Exhibit Promising Potential for Supporting Cardiac Repair in Vitro

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