c-kit
            <sup>+</sup>
            Cardiac Stem Cells

Khan, Mohsin; Koch, Walter J.

doi:10.1161/circresaha.115.308103

Cited by 10 publications

(4 citation statements)

References 20 publications

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“…Myocardial repair and regeneration research continues to progress on multiple fronts supported by over a decade of cumulative studies despite a recent "whipsaw" movement of controversies related to the terminology and biology of "cardiac stem cells." 30,31 Although cardiogenic potential of cardiac stem cells remains debatable, 32,33 cardioprotective effects have been repeatedly demonstrated by our group and others, 13,[34][35][36] with cardiac stem cells now referred to as cCIC in this article to avoid being misconstrued as cardiogenic cells. Furthermore, cardioprotective effects of cCICs are enhanced by combinatorial delivery with MSCs.…”

Section: Discussionmentioning

confidence: 83%

Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell

Firouzi

Choudhury

Broughton

et al. 2020

JAHA

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Background CardioChimeras produced by fusion of murine c‐kit + cardiac interstitial cells with mesenchymal stem cells promote superior structural and functional recovery in a mouse model of myocardial infarction compared with either precursor cell alone or in combination. Creation of human CardioChimeras ( hCCs ) represents the next step in translational development of this novel cell type, but new challenges arise when working with c‐kit + cardiac interstitial cells isolated and expanded from human heart tissue samples. The objective of the study was to establish a reliable cell fusion protocol for consistent optimized creation of hCC s and characterize fundamental hCC properties. Methods and Results Cell fusion was induced by incubating human c‐kit + cardiac interstitial cells and mesenchymal stem cells at a 2:1 ratio with inactivated Sendai virus. Hybrid cells were sorted into 96‐well microplates for clonal expansion to derive unique cloned hCC s, which were then characterized for various cellular and molecular properties. hCC s exhibited enhanced survival relative to the parent cells and promoted cardiomyocyte survival in response to serum deprivation in vitro. Conclusions The generation of hCC is demonstrated and validated in this study, representing the next step toward implementation of a novel cell product for therapeutic development. Feasibility of creating human hybrid cells prompts consideration of multiple possibilities to create novel chimeric cells derived from cells with desirable traits to promote healing in pathologically damaged myocardium.

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Section: Discussionmentioning

confidence: 83%

Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell

Firouzi

Choudhury

Broughton

et al. 2020

JAHA

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“…Others have suggested the role of stem cell progenitor cells, such as the c‐kit+ cardiac stem cells (Bearzi et al, 2007; Beltrami et al, 2003). However, the contribution of c‐kit+ cardiac stem cells in cardiomyocyte renewal has been controversial (Bearzi et al, 2007; Bergmann et al, 2009; Elhelaly et al, 2019; Jesty et al, 2012; Khan & Koch, 2016; Kikuchi et al, 2010; Porrello et al, 2013; Senyo et al, 2013; Sultana et al, 2015; van Berlo et al, 2014).…”

Section: Pre‐existing Cardiomyocytes Are the Major Source Of New Card...mentioning

confidence: 99%

Two decades of heart regeneration research: Cardiomyocyte proliferation and beyond

Huang,

Payumo

2023

WIREs Mechanisms of Disease

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Interest in vertebrate cardiac regeneration has exploded over the past two decades since the discovery that adult zebrafish are capable of complete heart regeneration, contrasting the limited regenerative potential typically observed in adult mammalian hearts. Undercovering the mechanisms that both support and limit cardiac regeneration across the animal kingdom may provide unique insights in how we may unlock this capacity in adult humans. In this review, we discuss key discoveries in the heart regeneration field over the last 20 years. Initially, seminal findings revealed that pre‐existing cardiomyocytes are the major source of regenerated cardiac muscle, drawing interest into the intrinsic mechanisms regulating cardiomyocyte proliferation. Moreover, recent studies have identified the importance of intercellular interactions and physiological adaptations, which highlight the vast complexity of the cardiac regenerative process. Finally, we compare strategies that have been tested to increase the regenerative capacity of the adult mammalian heart.This article is categorized under: Cardiovascular Diseases > Stem Cells and Development

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“…While this is an important question, it does not address the full regenerative potential of CPCs. In fact, regeneration of myocardial tissue is improved by exogenous cell implantation [ 6 – 8 ]. CPCs as cell therapy in ischemic heart disease have a measurable cardiac benefit in the clinic [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro

French

Maxwell

Bhutani

et al. 2016

Stem Cells International

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Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2–4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment.

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c-kit ⁺ Cardiac Stem Cells

Cited by 10 publications

References 20 publications

Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell

Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell

Two decades of heart regeneration research: Cardiomyocyte proliferation and beyond

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro

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c-kit + Cardiac Stem Cells

Cited by 10 publications

References 20 publications

Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell

Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell

Two decades of heart regeneration research: Cardiomyocyte proliferation and beyond

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro

Contact Info

Product

Resources

About

c-kit ⁺ Cardiac Stem Cells