Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice.
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.
Vascular Biology Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Zia A
ZA
Khan
Elisa
E
Boscolo
Arnaud
A
Picard
Sarah
S
Psutka
Juan M
JM
Melero-Martin
Tatianna C
TC
Bartch
John B
JB
Mulliken
Joyce
J
Bischoff
D017667:Adipocytes / Q000737:chemistry / Q000473:pathology; D000818:Animals; D034961:Antigens, Nuclear / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology; D051272:Glucose Transporter Type 1 / Q000032:analysis; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006391:Hemangioma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D007797:Laminin / Q000032:analysis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D039902:Multipotent Stem Cells / Q000737:chemistry / Q000473:pathology / Q000637:transplantation*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology / Q000637:transplantation*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D014162:Transfection
D034961:Antigens, Nuclear; D000954:Antigens, Surface; D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; D007797:Laminin; D000070778:Perilipin-1; D010750:Phosphoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C485192:green fluorescent protein, Aequorea victoria; D049452:Green Fluorescent Proteins; D040262:Receptors, Vascular Endothelial Growth Factor