Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

“…Overall, CMN colonies could be maintained for at least 84 days in vitro. Similarly, tumor-propagating cells have been reported in other benign cutaneous proliferations such as papilloma and hemangioma (Khan et al, 2008;Xu et al, 2011;Lapouge et al, 2012). Beyond in vitro studies, maintaining properties were studied in vivo.…”

Section: Discussionmentioning

confidence: 95%

Clonogenic Cell Subpopulations Maintain Congenital Melanocytic Nevi

Charbel

Fontaine

Kadlub

et al. 2015

Journal of Investigative Dermatology

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Large congenital melanocytic nevi (lCMN) are benign melanocytic tumors associated with an increased risk of melanoma transformation. They result predominantly from a post-zygotic somatic NRAS mutation. These lesions persist and even increase after birth proportionally to the child's growth. Therefore, we asked here whether cells with clonogenic and tumorigenic properties persisted postnatally in lCMN. Subpopulations of lCMN cells expressed stem cell/progenitor lineage markers such as Sox10, Nestin, Oct4, and ABCB5. In vitro, 1 in 250 cells from fresh lCMN formed colonies that could be passaged and harbored the same NRAS mutation as the original nevus. In vivo, lCMN specimens xenografted in immunocompromised mice expanded 4-fold. BrdU(+)-proliferating and label-retaining melanocytes were found within the outgrowth skin tissue of these xenografts, which displayed the same benign nested architecture as the original nevus. lCMN cell suspensions were not able to expand when xenografted alone in Rag 2-/- mice. Conversely, when mixed with keratinocytes, these cells reconstituted the architecture of the human nevus with its characteristic melanocyte layout, lentiginous hyperplasia, and nested architecture. Overall, our data demonstrate that, after birth, certain lCMN cell subtypes still display features such as clonogenic potential and expand into nevus-like structures when cooperating with adjacent keratinocytes.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

2014

Cancer Cell Signaling

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Infantile hemangioma (IH), which is the most common tumor in infants, is a benign vascular neoplasm resulting from the abnormal proliferation of endothelial cells and pericytes. For nearly a century, researchers have noted that IH exhibits diverse and often dramatic clinical behaviors. On the one hand, most lesions pose no threat or potential for complication and resolve spontaneously without concern in most children with IH. On the other hand, approximately 10% of IHs are destructive, disfiguring and even vision-or life-threatening. Recent studies have provided some insight into the pathogenesis of these vascular tumors, leading to a better understanding of the biological features of IH and, in particular, indicating that during hemangioma neovascularization, two main pathogenic mechanisms prevail, angiogenesis and vasculogenesis. Both mechanisms have been linked to alterations in several important cellular signaling pathways. These pathways are of interest from a therapeutic perspective because targeting them may help to reverse, delay or prevent hemangioma neovascularization. In this review, we explore some of the major pathways implicated in IH, including the VEGF/VEGFR, Notch, β-adrenergic, Tie2/angiopoietins, PI3K/AKT/mTOR, HIF-α-mediated and PDGF/PDGF-R-β pathways. We focus on the role of these pathways in the pathogenesis of IH, how they are altered and the consequences of these abnormalities. In addition, we review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against some of these pathways.

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Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

Cited by 46 publications

References 29 publications

Educational paper: pathogenesis of infantile haemangioma, an update 2014 (part I)

Educational paper: pathogenesis of infantile haemangioma, an update 2014 (part I)

Clonogenic Cell Subpopulations Maintain Congenital Melanocytic Nevi

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

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