Infantile Hemangioma Originates From A Dysregulated But Not Fully Transformed Multipotent Stem Cell

Harbi, Shaghayegh; Wang, Rong; Gregory, Mike; Hanson, Nicole; Kobylarz, Keith; Ryan, Kamilah; Deng, Yan; Lopez, Peter; Chiriboga, Luis; Mignatti, Paolo

doi:10.1038/srep35811

Cited by 31 publications

(34 citation statements)

References 88 publications

(126 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until now, the etiopathogenesis of IH growth and involution have not been well understood. Recent studies have identified haemangioma‐derived stem cells (HemSCs) as the cellular origin of IH . Some genetic and biochemical data have also shown that IH originates from dysregulated but not fully transformed multipotent stem cells and expresses genes associated with vasculogenesis, angiogenesis, tumorigenesis and associated signalling pathways …”

Section: Introductionmentioning

confidence: 99%

NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma

Byun

Yeom

et al. 2018

Experimental Dermatology

View full text Add to dashboard Cite

The etiopathogenesis of infantile haemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal haemangioma capillary formation. The role of NDRG1, a hypoxia-inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile haemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile haemangioma and the correlation of these proteins with proliferation and involution. Primary endothelial cells were obtained, with parental agreement, from 12 infantile haemangioma patients during surgery; 6 patients had proliferating infantile haemangiomas and 6 had involuting IHs. We compared the infantile haemangioma tissues and primary endothelial cells with human vein endothelial cells using microarrays, real-time PCR, Western blotting and immunohistochemical staining. Our data indicated that FOXO1 expression was downregulated in proliferating infantile haemangioma tissue. We found that the expression of NDRG1, a molecule upstream of the FOXO1 pathway, increased during haemangioma proliferation. NDRG1 knockdown decreased haemangioma endothelial cell proliferation and downregulated c-MYC oncoprotein levels. Our findings suggest that NDRG1 positively regulates haemangioma proliferation. FOXO1 dysregulation plays an important role in infantile haemangiomas pathogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma

Byun

Yeom

et al. 2018

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…Hemscs are considered to be responsible for IH since Hemscs have the potential to divide into other different cell components of IHs. Multilineage differentiation potential assay were shown in Figure D . Positive Alizarin Red S staining and Oil Red O staining showed osteogenetic and adipogenic differentiation of Hemscs.…”

Section: Resultsmentioning

confidence: 96%

Propranolol‐Loaded Mesoporous Silica Nanoparticles for Treatment of Infantile Hemangiomas

Wang

Zheng

et al. 2019

Adv Healthcare Materials

View full text Add to dashboard Cite

birth-weight, and premature infants. [3] The cause of IH onset has not been well elucidated, but IH has proven to be a disorder of angiogenesis and vasculogenesis with excessive proliferation of microvessels. [4] IH is often characterized by unique growth pattern with rapid proliferating phrase followed by spontaneous involution. [5] Due to the benign nature and tendency to resolve spontaneously, a "wait and see" strategy persisted in the past. However, some untreated IH will leave permanent changes, such as telangiectasias, scarring, skin atrophy, and fibro-fatty residual. Furthermore, about 10% of IH are destructive and problematic with the increasing risk for disfigurement and functional impairment. [6] Therefore, more active management in IH therapy instead of observation are often suggested by pediatricians. Currently, there are mainly three kinds of treatment methods for IHs, including drug therapy, laser therapy, and surgery. The individual treatment plan should be made according to the location, extent, depth, and biological phrase of the lesion and techniques available. [7] Given the discovery of its remarkable efficacy in treating proliferating IH since 2008, beta-adrenergic receptor blocker propranolol (PRN) has been widely used as the first-line therapy for IH. A great number of clinical studies (including retrospective study, prospective study, and meta-analysis) demon strated the efficacy of PRN in treating IH. [8] However, the bioavailability of PRN therapy in IH is always unsatisfactory. Our group previously investigated the pharmacokinetics of propranolol, and discovered that the peak plasma concentration of PRN was 383 ng mL −1 after administration of 1 mg kg −1 propranolol, and the elimination half-life was about 6 h. [9] Furthermore, PRN therapy for IH has been controversial due to the side effects. Although the short-term side effects are usually selflimiting and easy to manage, [10] such as bradycardia, bronchospasm, hypotension, hypoglycemia, electrolyte disturbances, and diarrhea, concerns regarding long-term neurocognitive effects have been raised recently due to the potentiality to penetrate the blood-brain-barrier and affect the central nervous system. [11] Consequently, there is an urgency to develop new approaches that could elevate the bioavailability of propranolol, extend the circulation time and lower the systemic toxicity of the drug.With the rapid development in nanotechnology, it is expected that novel treatments based on nanomedicine would be applied in the clinical practice in the near future. In the way of Infantile hemangioma (IH) is one of the most common neoplasm of infancy.Although with the potential to involute slowly after proliferation, IH has several subsets that could develop severe complications and lead to functional impairment or permanent disfigurement. In the present study, a novel propranolol (PRN) delivery system is developed that encapsulated in mesoporous silica nanoparticles (MSN). The primary nanoparticles are further treated with polyvinyl alcohol (PVA) ...

show abstract

“…The embryonic origins of IH remain unknown, in spite of much research. Multipotent dysregulated progenitor‐like, hemangioma‐derived stem cell (HemSC) proposed to give rise to IH do express mesenchymal markers (CD90) . Thus, developmental errors in mesenchymal precursors with similar migration patterns may explain the shared biker‐glove morphology between CMN and IH.…”

Section: Discussionmentioning

confidence: 99%

The biker‐glove pattern of congenital melanocytic nevi

Kittler

Mathes

Kinsler

et al. 2019

Pediatric Dermatology

View full text Add to dashboard Cite

Congenital melanocytic nevi (CMN) are common birthmarks with 20% occurring on the limbs. We describe 4 patients with acral CMN with a “biker‐glove” distribution with sparing of the distal digits, as has previously been described in acral infantile hemangiomas (IH). The existence of the biker‐glove pattern suggests that CMN arise from early mutations in melanocyte precursors and supports the recently described Kinsler‐Larue hypothesis of mesenchymal distribution of melanocyte migration occurring in a circular field from a central point. Developmental errors in mesenchymal precursors with similar migration patterns may explain this shared pattern among CMN and IH.

show abstract

Infantile Hemangioma Originates From A Dysregulated But Not Fully Transformed Multipotent Stem Cell

Cited by 31 publications

References 88 publications

NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma

NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma

Propranolol‐Loaded Mesoporous Silica Nanoparticles for Treatment of Infantile Hemangiomas

The biker‐glove pattern of congenital melanocytic nevi

Contact Info

Product

Resources

About