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Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice
Zia A. Khan, Elisa Boscolo, Arnaud Picard, Sarah Psutka, Juan M. Melero-Martin, Tatianna C. Bartch, John B. Mulliken, Joyce Bischoff
Zia A. Khan, Elisa Boscolo, Arnaud Picard, Sarah Psutka, Juan M. Melero-Martin, Tatianna C. Bartch, John B. Mulliken, Joyce Bischoff
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Research Article Angiogenesis

Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice

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Abstract

Infantile hemangioma is a benign endothelial tumor composed of disorganized blood vessels. It exhibits a unique life cycle of rapid postnatal growth followed by slow regression to a fibrofatty residuum. Here, we have reported the isolation of multipotential stem cells from hemangioma tissue that give rise to hemangioma-like lesions in immunodeficient mice. Cells were isolated based on expression of the stem cell marker CD133 and expanded from single cells as clonal populations. The CD133-selected cells generated human blood vessels 7 days after implantation in immunodeficient mice. Cell retrieval experiments showed the cells could again form vessels when transplanted into secondary recipients. The human vessels expressed GLUT-1 and merosin, immunodiagnostic markers for infantile hemangioma. Two months after implantation, the number of blood vessels diminished and human adipocytes became evident. Lentiviral expression of GFP was used to confirm that the hemangioma-derived cells formed the blood vessels and adipocytes in the immunodeficient mice. Thus, when transplanted into immunodeficient mice, hemangioma-derived cells recapitulated the unique evolution of infantile hemangioma — the formation of blood vessels followed by involution to fatty tissue. In summary, this study identifies a stem cell as the cellular origin of infantile hemangioma and describes for what we believe is the first time an animal model for this common tumor of infancy.

Authors

Zia A. Khan, Elisa Boscolo, Arnaud Picard, Sarah Psutka, Juan M. Melero-Martin, Tatianna C. Bartch, John B. Mulliken, Joyce Bischoff

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Figure 5

HemSCs form adipocytes in vivo.

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HemSCs form adipocytes in vivo.
(A) Clonal HemSCs were suspended in Matr...
(A) Clonal HemSCs were suspended in Matrigel and injected s.c. into nude mice for 7, 14, 28, and 56 days, as shown in Figure 3A. Blood vessels, identified in H&E sections as luminal structures containing rbc, were quantified at the 4 time points. *P < 0.05 compared with other time points. (B) GFP-labeled HemSCs were implanted as described in Figure 4 and analyzed after 56 days for expression of GFP and the adipocyte marker perilipin A. Right panel shows the merged image, middle panel shows GFP (green), and right panel shows perilipin A (red); all panels were stained with DAPI. (C) Sections from the 28-day time point were immunostained with an anti-human nuclear antigen antibody using an HRP-conjugated secondary antibody and a diaminobenzidine substrate. Mouse heart tissue sections showed no immunostaining while nuclei in human hemangioma tissue were uniformly positive, confirming the specificity of anti-human nuclear antigen. Scale bars: 50 μM.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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