Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice

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.

RCT of Timolol Maleate Gel for Superficial Infantile Hemangiomas in 5- to 24-Week-Olds

“…Efficacy was assessed by performing blinded volume measurements at weeks 0, 1, 2, 3,4,8,12,16,20, and 24 and blinded investigator photograph scoring at weeks 0, 12, and 24. Safety was assessed by measuring heart rate and systolic and diastolic blood pressure at weeks 0, 1, 2, 3,4,8,12,16,20, and 24.…”

“…Pediatrics 2013;131:e1739-e1747 Infantile hemangiomas (IHs) are among the most common tumors of infancy, with ∼4% of infants affected. [1][2][3] Khan et al 4 reported that IHs arise from CD133 + stem cells, which can differentiate into several cell lineages including adipocytes. The mechanisms that control the proliferation and involution of these lesions are not as yet fully understood.…”

Wnt3a Expression is Associated with MMP-9 Expression in Primary Tumor and Metastatic Site in Recurrent or Stage IV Colorectal Cancer

“…In the past decade, hemangioma-derived progenitor/stem cells (HemSCs), mesenchymal stem cells (Hem-MSCs), endothelial progenitor cells (HemEPCs), ECs (HemECs) and perivascular cells (Hem-pericytes), all of which comprise the IH, have been isolated (Table 1) [15][16][17][18]. In general, CD133 was used as a stem cell biomarker for the isolation of HemSCs from IH tissues.…”

“…Therefore, HemSCs may contain both of Hem-MSCs and HemEPCs. Studies from different groups have demonstrated that HemSCs have the ability to self-renew and can differentiate into endothelium, adipocytes and pericytes in vitro [15,20]. When implanted subcutaneously into nude mice, HemSCs can produce human glucose transporter-1 (GLUT-1) positive microvessels at 7-14 days [15,[20][21][22].…”

Pulse steroid therapy in infantile facial hemangiomas: the early experience

“…The mechanism of action of steroids is not entirely clear, though it is postulated to have an inhibitory effect on the production of vascular endothelial growth factor A (VEGF-A) by stem cells in haemangioma. 13,14 This is the study to demonstrate the efficacy of corticosteroids in halting the proliferation of IHs clinically (decrease in hemangioma size and improved visual function) and biologically (decrease in the circulating proangiogenic proteins). The effect, measured over the first year of life, was more pronounced with high-dose, intermittent pulses with methylprednisolone.…”