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Atrial Myxomas Arise From Multipotent Cardiac Stem Cells

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Atrial Myxomas Arise From Multipotent Cardiac Stem Cells. / Scalise, Mariangela; Torella, Michele; Marino, Fabiola; Ravo, Maria; Giurato, Giorgi; Vicinanza, Carla; Cianflone, Eleonora; Mancuso, Teresa; Aquila, Iolanda; Salerno, Luca; Nassa, Giovanni; Agosti, Valter; De Angelis, Antonella; Urbanek, Konrad; Veltri, Pierangelo; Paolino, Donatella; Mastroroberto, Pasquale; De Feo, Marisa; Viglietto, Giuseppe; Weisz, Alessandro; Nadal-Ginard, Bernardo; Ellison-Hughes, Georgina M.; Torella, Daniele.

In: European Heart Journal, 24.04.2020.

Research output: Contribution to journalArticle

Harvard

Scalise, M, Torella, M, Marino, F, Ravo, M, Giurato, G, Vicinanza, C, Cianflone, E, Mancuso, T, Aquila, I, Salerno, L, Nassa, G, Agosti, V, De Angelis, A, Urbanek, K, Veltri, P, Paolino, D, Mastroroberto, P, De Feo, M, Viglietto, G, Weisz, A, Nadal-Ginard, B, Ellison-Hughes, GM & Torella, D 2020, 'Atrial Myxomas Arise From Multipotent Cardiac Stem Cells', European Heart Journal. https://doi.org/10.1093/eurheartj/ehaa156, https://doi.org/10.1093/eurheartj/ehaa156

APA

Scalise, M., Torella, M., Marino, F., Ravo, M., Giurato, G., Vicinanza, C., ... Torella, D. (2020). Atrial Myxomas Arise From Multipotent Cardiac Stem Cells. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaa156, https://doi.org/10.1093/eurheartj/ehaa156

Vancouver

Scalise M, Torella M, Marino F, Ravo M, Giurato G, Vicinanza C et al. Atrial Myxomas Arise From Multipotent Cardiac Stem Cells. European Heart Journal. 2020 Apr 24. https://doi.org/10.1093/eurheartj/ehaa156, https://doi.org/10.1093/eurheartj/ehaa156

Author

Scalise, Mariangela ; Torella, Michele ; Marino, Fabiola ; Ravo, Maria ; Giurato, Giorgi ; Vicinanza, Carla ; Cianflone, Eleonora ; Mancuso, Teresa ; Aquila, Iolanda ; Salerno, Luca ; Nassa, Giovanni ; Agosti, Valter ; De Angelis, Antonella ; Urbanek, Konrad ; Veltri, Pierangelo ; Paolino, Donatella ; Mastroroberto, Pasquale ; De Feo, Marisa ; Viglietto, Giuseppe ; Weisz, Alessandro ; Nadal-Ginard, Bernardo ; Ellison-Hughes, Georgina M. ; Torella, Daniele. / Atrial Myxomas Arise From Multipotent Cardiac Stem Cells. In: European Heart Journal. 2020.

Bibtex Download

@article{c461b92d7bc2497882c8544e30fb9224,
title = "Atrial Myxomas Arise From Multipotent Cardiac Stem Cells",
abstract = "Aims: Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumors are a valuable research model because of the rarity of cardiac tumors, their clinical presentation and uncertain origin. Here, we assessed whether human adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells. Methods and Results: 23 myxomas were collected and processed/analyzed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately <10{\%} of the c-kitpos/ CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. They exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to c-kitpos/CD45neg /CD31neg CSCs isolated from normal myocardial tissue. Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumors in xenograft’s in NOD/SCID mice. Conclusion: Myxoma-derived c-kitpos/CD45neg /CD31neg fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg /CD31neg CSCs. Taken together the data presented here suggests that human myxomas are the first-described CSC-related human cardiac disease.",
keywords = "Myxoma, Tumor Histogenesis, Adult Cardiac Stem Cells, RNASeq, microRNA",
author = "Mariangela Scalise and Michele Torella and Fabiola Marino and Maria Ravo and Giorgi Giurato and Carla Vicinanza and Eleonora Cianflone and Teresa Mancuso and Iolanda Aquila and Luca Salerno and Giovanni Nassa and Valter Agosti and {De Angelis}, Antonella and Konrad Urbanek and Pierangelo Veltri and Donatella Paolino and Pasquale Mastroroberto and {De Feo}, Marisa and Giuseppe Viglietto and Alessandro Weisz and Bernardo Nadal-Ginard and Ellison-Hughes, {Georgina M.} and Daniele Torella",
year = "2020",
month = "4",
day = "24",
doi = "10.1093/eurheartj/ehaa156",
language = "English",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Atrial Myxomas Arise From Multipotent Cardiac Stem Cells

AU - Scalise, Mariangela

AU - Torella, Michele

AU - Marino, Fabiola

AU - Ravo, Maria

AU - Giurato, Giorgi

AU - Vicinanza, Carla

AU - Cianflone, Eleonora

AU - Mancuso, Teresa

AU - Aquila, Iolanda

AU - Salerno, Luca

AU - Nassa, Giovanni

AU - Agosti, Valter

AU - De Angelis, Antonella

AU - Urbanek, Konrad

AU - Veltri, Pierangelo

AU - Paolino, Donatella

AU - Mastroroberto, Pasquale

AU - De Feo, Marisa

AU - Viglietto, Giuseppe

AU - Weisz, Alessandro

AU - Nadal-Ginard, Bernardo

AU - Ellison-Hughes, Georgina M.

AU - Torella, Daniele

PY - 2020/4/24

Y1 - 2020/4/24

N2 - Aims: Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumors are a valuable research model because of the rarity of cardiac tumors, their clinical presentation and uncertain origin. Here, we assessed whether human adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells. Methods and Results: 23 myxomas were collected and processed/analyzed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately <10% of the c-kitpos/ CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. They exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to c-kitpos/CD45neg /CD31neg CSCs isolated from normal myocardial tissue. Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumors in xenograft’s in NOD/SCID mice. Conclusion: Myxoma-derived c-kitpos/CD45neg /CD31neg fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg /CD31neg CSCs. Taken together the data presented here suggests that human myxomas are the first-described CSC-related human cardiac disease.

AB - Aims: Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumors are a valuable research model because of the rarity of cardiac tumors, their clinical presentation and uncertain origin. Here, we assessed whether human adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells. Methods and Results: 23 myxomas were collected and processed/analyzed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately <10% of the c-kitpos/ CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. They exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to c-kitpos/CD45neg /CD31neg CSCs isolated from normal myocardial tissue. Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumors in xenograft’s in NOD/SCID mice. Conclusion: Myxoma-derived c-kitpos/CD45neg /CD31neg fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg /CD31neg CSCs. Taken together the data presented here suggests that human myxomas are the first-described CSC-related human cardiac disease.

KW - Myxoma, Tumor Histogenesis, Adult Cardiac Stem Cells, RNASeq, microRNA

U2 - 10.1093/eurheartj/ehaa156

DO - 10.1093/eurheartj/ehaa156

M3 - Article

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

ER -

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