Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model
<p>Abstract</p> <p>Background</p> <p>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 throu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-12-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://www.jhoonline.org/content/4/1/54 |
| _version_ | 1818068137276342272 |
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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 | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH.</p> <p>Results</p> <p>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 <it>in vitro</it>. 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 <it>in vitro</it>. 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.</p> <p>Conclusions</p> <p>The ability to propagate large numbers of IH stem cells <it>in vitro </it>and the generation of an <it>in vivo </it>mouse model provides novel avenues for testing IH therapeutic agents in the future.</p> |
| first_indexed | 2024-12-10T15:34:47Z |
| format | Article |
| id | doaj.art-ec01081bc8d14bf6a4369a57475e5158 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-10T15:34:47Z |
| publishDate | 2011-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-ec01081bc8d14bf6a4369a57475e51582022-12-22T01:43:16ZengBMCJournal of Hematology & Oncology1756-87222011-12-01415410.1186/1756-8722-4-54Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse modelXu DanO Teresa MShartava ArchilFowles Taylor CYang JianchangFink Louis MWard David CMihm Martin CWaner MiltonMa Yupo<p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH.</p> <p>Results</p> <p>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 <it>in vitro</it>. 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 <it>in vitro</it>. 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.</p> <p>Conclusions</p> <p>The ability to propagate large numbers of IH stem cells <it>in vitro </it>and the generation of an <it>in vivo </it>mouse model provides novel avenues for testing IH therapeutic agents in the future.</p>http://www.jhoonline.org/content/4/1/54Infantile hemangiomastem cellstumor spheresSALL4 |
| spellingShingle | 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 <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model Journal of Hematology & Oncology Infantile hemangioma stem cells tumor spheres SALL4 |
| title | Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model |
| title_full | Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model |
| title_fullStr | Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model |
| title_full_unstemmed | Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model |
| title_short | Isolation, characterization, and <it>in vitro </it>propagation of infantile hemangioma stem cells and an <it>in vivo </it>mouse model |
| title_sort | isolation characterization and it in vitro it propagation of infantile hemangioma stem cells and an it in vivo it mouse model |
| topic | Infantile hemangioma stem cells tumor spheres SALL4 |
| url | http://www.jhoonline.org/content/4/1/54 |
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