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

Journal of Hematology & Oncology

Yupo Ma³  Milton Waner¹  Martin C Mihm⁴  David C Ward⁵  Louis M Fink²  Jianchang Yang²  Taylor C Fowles²  Archil Shartava²  Teresa M O¹  Dan Xu² 

[1] Vascular Birthmark Institute of New York, New York, NY 10023, USA;Division of Laboratory Medicine, Nevada Cancer Institute, 1 Breakthrough Way, Las Vegas, NV 89135, USA;Biopharmaceutical Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China;Massachusetts General Hospital, Dermatopathology, Boston, MA 02114, USA;Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 9681, USA

关键词: SALL4;    tumor spheres;    stem cells;    Infantile hemangioma;   

Others  :  826014
DOI  :  10.1186/1756-8722-4-54

 received in 2011-11-08, accepted in 2011-12-22,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Xu et al; licensee BioMed Central Ltd.

【 图 表 】

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