Mesenchymal Stem Cells and Adipogenesis in Hemangioma Involution

Abstract

Hemangioma is a benign tumor of infancy whose hallmark is rapid growth during the first year of life followed by slow regression during early childhood. The proliferating phase is characterized by abundant immature endothelial cells, the involuting phase by prominent endothelial-lined vascular channels and endothelial apoptosis, and the involuted phase by few remaining capillary-like vessels surrounded by loose fibrofatty tissue. Nothing is known about the mechanisms that contribute to the adipogenesis during this spontaneous regression. We postulated that mesenchymal stem cells (MSCs) reside in the tumor and preferentially differentiate into adipocytes. To test this hypothesis, we isolated MSCs from 14 proliferating and five involuting hemangiomas by taking advantage of the well known selective adhesion of MSCs to bacteriologic dishes. These hemangioma-derived MSCs (Hem-MSCs) are similar to MSCs obtained from human bone marrow, expressing the cell surface markers SH2 (CD105), SH3, SH4, CD90, CD29, smooth muscle ␣-actin, and CD133 but not the hematopoietic markers CD45 and CD14 or the hematopoietic/endothelial markers CD34, CD31, and kinase insert domain receptor (KDR). HemMSCs exhibited multilineage differentiation with robust adipogenic potential that correlated with the proliferating phase. The numbers of adipogenic Hem-MSCs were higher in proliferating-phase than in involuting-phase tumors and higher than in normal infantile skin. Furthermore, HemMSCs exhibited a random pattern of X-chromosomal inactivation, indicating that these cells are not clonally derived. In summary, we have identified MSCs as a novel cellular constituent in infantile hemangioma. These MSCs may contribute to the adipogenesis during hemangioma involution.

Autologous Mesenchymal Stromal Cells and Kidney Transplantation

“…The contribution of MSCs in the development of hemangiomas on native kidney in patient 2 remains ill defined. Paracrine mechanisms may favor endothelial proliferation, whereas MSC differentiation into adipocytes may contribute to adipogenesis during hemangioma involution (42). However, these lesions could also be accidental findings unrelated to MSC infusion.…”

Diagnosis and Management of Infantile Hemangioma

“…42 The concept that IHs originate from circulating multipotent progenitor cells could explain some of the features they share with placental blood vessels, because dysregulated circulating EPCs have also been implicated in many of the associated maternal and fetal comorbid conditions (preeclampsia, retinopathy of prematurity, etc). HemSCs have also been shown to have an adipogenic potential, 43 which may explain the presence of adipocytes noted during involution. The stimulus for division of EPCs is unknown but may be a somatic mutation or abnormal signals from local tissues.…”

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.…”