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Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

BACKGROUND: Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to...

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Autores principales: Xu, Dan, O, Teresa M, Shartava, Archil, Fowles, Taylor C, Yang, Jianchang, Fink, Louis M, Ward, David C, Mihm, Martin C, Waner, Milton, Ma, Yupo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259074/
https://www.ncbi.nlm.nih.gov/pubmed/22192404
http://dx.doi.org/10.1186/1756-8722-4-54
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author Xu, Dan
O, Teresa M
Shartava, Archil
Fowles, Taylor C
Yang, Jianchang
Fink, Louis M
Ward, David C
Mihm, Martin C
Waner, Milton
Ma, Yupo
author_facet Xu, Dan
O, Teresa M
Shartava, Archil
Fowles, Taylor C
Yang, Jianchang
Fink, Louis M
Ward, David C
Mihm, Martin C
Waner, Milton
Ma, Yupo
author_sort Xu, Dan
collection PubMed
description BACKGROUND: Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an in vitro cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH. RESULTS: We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells in vitro. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth in vitro. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas. CONCLUSIONS: The ability to propagate large numbers of IH stem cells in vitro and the generation of an in vivo mouse model provides novel avenues for testing IH therapeutic agents in the future.
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spelling pubmed-32590742012-01-17 Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model Xu, Dan O, Teresa M Shartava, Archil Fowles, Taylor C Yang, Jianchang Fink, Louis M Ward, David C Mihm, Martin C Waner, Milton Ma, Yupo J Hematol Oncol Research BACKGROUND: Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an in vitro cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH. RESULTS: We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells in vitro. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth in vitro. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas. CONCLUSIONS: The ability to propagate large numbers of IH stem cells in vitro and the generation of an in vivo mouse model provides novel avenues for testing IH therapeutic agents in the future. BioMed Central 2011-12-22 /pmc/articles/PMC3259074/ /pubmed/22192404 http://dx.doi.org/10.1186/1756-8722-4-54 Text en Copyright ©2011 Xu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Xu, Dan
O, Teresa M
Shartava, Archil
Fowles, Taylor C
Yang, Jianchang
Fink, Louis M
Ward, David C
Mihm, Martin C
Waner, Milton
Ma, Yupo
Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
title Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
title_full Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
title_fullStr Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
title_full_unstemmed Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
title_short Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
title_sort isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259074/
https://www.ncbi.nlm.nih.gov/pubmed/22192404
http://dx.doi.org/10.1186/1756-8722-4-54
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