Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells

Itzhaki-Alfia, Ayelet; Leor, Jonathan; Raanani, Ehud; Sternik, Leonid; Spiegelstein, Dan; Netser, Shiri; Holbová, Radka; Pevsner‐Fischer, Meirav; Lavee, Jacob; Barbash, Israel M.

doi:10.1161/circulationaha.109.849588

Cited by 120 publications

(139 citation statements)

References 27 publications

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“…The availability of sheep CPC will provide new opportunities to Isl1+precursors have the potential of self-renewal and differentiation into endothelial, cardiomyocyte, and smooth muscle lineages [23]. Cardiovascular progenitor cells that express Isl1 were shown to cluster within the right atrial wall in fetal and newborn humans [22], but occurred at lower frequency when compared with our findings in sheep of comparable age [24]. All CPC clones isolated from neonatal sheep expressed Isl1, possibly due to the method of progenitor cell isolation used in our study which allowed us to examine transcription factor expression in proliferating cardiovascular cell clones.…”

Section: Discussionsupporting

confidence: 48%

“…Sheep CPC that are c-kit+Isl1+ and c-kit-isl1+ are present and clonable in normal sheep. Interestingly, sheep CPC can co-express c-kit and Isl1 whereas, a CPC population expressing c-kit and Isl1 has not been identified in humans [24,29]. As some c-kit+ cells also may be mast cells [29], the frequent co-expression of Isl1 and c-kit in our study indicates that c-kit positive cells in the sheep heart are cardiovascular progenitors.…”

Section: Discussionmentioning

confidence: 55%

“…Although Isl1 expression is limited, a higher percentage of cardiovascular progenitors expressing c-kit can be isolated from human patients (approximately 24%) [24]. A similar percentage of c-kit expressing cells were identified in sheep.…”

Section: Discussionmentioning

confidence: 92%

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Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart

Hou

Appleby²,

Fuentes³

et al. 2013

J Clin Exp Cardiolog

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Background: Laboratory large animal models are important for establishing the efficacy of stem cell therapies that may be translated into clinical use. The similarity of ovine and human cardiovascular systems provides an opportunity to use the sheep as a large animal model in which to optimize cell-based treatments for the heart. Recent clinical trials in humans using endogenous cardiovascular progenitor cells report significant improvement in cardiac function following stem cell-based therapy. To date, however, endogenous cardiovascular progenitor cells have not been isolated from the sheep heart.Methods: Cardiovascular cells expressing SSEA-4, CD105 and c-kit were isolated by flow cytometry and cloned from the right atrium of neonatal sheep. The expression of GATA-4, c-kit, and Isl1 was identified by PCR in the cloned cells. Immunohistochemical staining was used to compare the number of SSEA-4 positive cells in the right auricle, right atrium, left ventricle and the apex of the heart of fetal, neonatal and adult sheep. The number of SSEA4+cells was also compared in fetal, pregnant and non-pregnant adult sheep. Results:Four distinct cardiac progenitor cell sub-populations were identified in sheep, including CD105+SSEA-4+c-kit+Isl1+GATA-4+cells, CD105+SSEA-4+c-kit+Isl1+GATA-4-cells, CD105+SSEA-4-c-kit-Isl1+GATA-4-cells, and CD105+SSEA-4-c-kit+Isl1+GATA-4-cells. Immunohistochemical staining for SSEA-4 showed that labeled cells were most abundant in the right atrium of fetal hearts where niches of progenitor cells could be identified. Conclusion:We determined the phenotype and distribution of cardiac progenitor cells in the sheep heart. The availability of cloned endogenous cardiac progenitor cells from sheep will provide a valuable resource for optimizing the conditions for cardiac repair in the ovine model.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 55%

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Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart

Hou

Appleby²,

Fuentes³

et al. 2013

J Clin Exp Cardiolog

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“…The fourth group remained untreated. At various time points after MI induction and treatment, hearts were harvested and underwent three 10-min cycles of enzymatic digestion using a cocktail of Dispase II and Trypsin-EDTA (22). The isolated cells were analyzed by FACS for the percentage of total macrophages (F4∕80 positive), the fraction of proinflammatory macrophages (F4∕80 positive cells expressing the proinflammatory marker CD86) and the fraction of reparative macrophages (F4∕80 positive cells expressing the mannose receptor CD206) (14,15).…”

Section: Induction Of Myocardial Infarction (Mi)mentioning

confidence: 99%

Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair

Harel-Adar

Mordechai

Amsalem

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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302

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Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-inflammatory cytokines [transforming growth factor β (TGFβ) and interleukin 10 (IL-10)] and upregulated the expression of the mannose receptor-CD206, concomitant with downregulation of proinflammatory markers, such as tumor necrosis factor α (TNFα) and the surface marker CD86. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging (MRI). The treatment promoted angiogenesis, the preservation of small scars, and prevented ventricular dilatation and remodeling. This strategy represents a unique and accessible approach for myocardial infarct repair.

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“…1) Cardiac stem cells (CSCs) are an attractive candidate for a source of cell therapy for patients with heart injury, because CSCs are of heart origin, 2) differentiate into cardiomyocytes, endothelial cells, or vascular cells, 1,3) and may contribute to endogenous cardiac repair. 4) A method to culture CSCs derived from adult heart tissue was established in 2004. 5) In this method, outgrowing cells that are expanded from cardiac specimens include a population that is positive for c-kit, a stem cell marker.…”

mentioning

confidence: 99%

Factors for C-Kit Expression in Cardiac Outgrowth Cells and Human Heart Tissue

et al. 2017

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Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells

Abstract: Our results show that the right atrium is the best source for c-kit(+) and Islet-1 progenitors, with higher percentages of c-kit(+) cells being produced by women.

Cited by 120 publications

References 27 publications

Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart

Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart

Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair

Factors for C-Kit Expression in Cardiac Outgrowth Cells and Human Heart Tissue

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