Mesenchymal Stem Cells in Infantile Hemangioma Reside in the Perivascular Region

Abstract

Infantile hemangioma grows quickly in the first year of life and regresses slowly to fibrofatty tissue during childhood; mesenchymal stem cells (MSCs) have been reported to contribute to this adipogenesis. Recent studies have shown the perivascular origin of MSCs in multiple organs. We hypothesized that MSCs in hemangioma might also reside in the perivascular region. We isolated MSCs from proliferating hemangioma by their selective adhesion to plastic culture dishes. Mesenchymal stem cells from bone marrow (BM-MSCs) and foreskin-derived fibroblasts were used as controls. Flow cytometry and immunofluorescence staining were used to examine their antigen profiles; in vitro induction of multi-lineage differentiation was performed to test their pluripotency. Platelet-derived growth factor R-β (PDGFR-β), CD133, and peroxisome-proliferator-activated receptor gamma (PPAR-γ) were selected as the markers to observe MSCs in hemangioma by immunohistochemistry staining, with costaining of CD31 and alpha-smooth muscle actin (α-SMA). Hemangioma-derived MSCs (Hem-MSCs) had fibroblast-like morphology; they expressed the MSC markers CD105, CD90, CD29, and vimentin and did not express the hematopoietic/endothelial markers CD45, CD34, CD31, and flt-1; Hem-MSCs also expressed CD133 and PPAR-γ. Most Hem-MSCs expressed PDGFR-β and α-SMA; in contrast, the expression of PDGFR-β and α-SMA in BM-MSCs was very weak. The Hem-MSCs differentiated into adipocytes, osteoblasts, and chondroblasts in vitro. This confirmed their pluripotency. Immunohistochemistry showed the colocalization of PDGFR-β/α-SMA, CD133/α-SMA, and PPAR-γ/α-SMA in the perivascular region. MSCs were successfully obtained from proliferating hemangioma, revealing the perivascular origin of MSCs in hemangioma.