Mechanisms Study On Infantile Hemangioma(IH) And The Treatment Choice For Superficial IH

ObjectivesInfantile hemangioma(IH)is defined as a benign vascular tumor composed of immature vascular endothelial cells,with the unique characteristics of richly vascularized and self-regressed into fibro-fatty tissue.CD133-positive Hemangioma Stem Cells(HemSCs),which exist in the proliferating infantile hemangioma tissue,was found to own the ability to establish infantile hemangioma animal model,and makes it to be the highlight in the pathogenesis of IHs in recent years.This study focused on the biological characteristics of HemSCs and aimed to provide more theoretic basis for the treatment.Superficial IHs are the most common type of IHs,and the treatment choice is various.Topical Timolol and 595nm pulsed-dye laser(PDL)are the most widely used to treat superficial IHs.However,to date,there is no reliable study to compare the therapeutic outcomes between the two treatment options directly.We designed the present study to evaluate and compare the efficacy and safety of Timolol cream and PDL in the treatment of superficial proliferating IHs.MethodsWe used FACS,in vitro induced differentiation,in vivo and in vitro angiogenesis assay and other techniques to study the surface markers,differential potential and angiogenesis potential of HemSC,and compared with these characteristics of MSCs,to further confirm our hypothesis.For the clinical trial,twenty-one patients with superficial IHs were included in the study.Each lesion was divided into two regions;one part was treated with 0.5%topical Timolol cream four times daily,and the other part was treated monthly with PDL.Both treatments were continued for 2-6 months.Five independent and blinded assessors were asked to judge the results in both the topical Timolol treated and PDL-treated parts by comparing photographs taken before and after treatment.ResultsWe successfully isolated and cultured HemSC.Our results confirmed that HemSC could differentiate into adipocyte and osteocyte.FACS results indicated that in average more than 80%of Passage 2-5 HemSC fit the criteria of MSC surface markers.In addition,the HemSC could also promote angiogenesis through para-secretion compared with fibroblast or MSC.Both treatments resulted in significant clinical improvements after 3.62 sessions in the 2-month follow-up.The average visual evaluation showed that PDL had significantly better results than topical Timolol(6.55±2.26 to 4.98±2.92,P<0.01).No patients experienced permanent side effects during the treatment.ConclusionsHemSC could originate from normal MSCs,and because of its powerful proliferation and angiogenesis ability,we considered it could be one of the base of the pathogenesis of IH.Meanwhile,these characteristics make it to be a great candidate seed cell in tissue engineering.For the superficial IH treatment,our shortterm study revealed that PDL had better results compared with topical Timolol cream application.However,the side-effect of topical Timolol is much slighter than PDL and because of it painlessness and convenient,so we still recommended topical Timolol as the first choice for superficial IHs.Further studies with longer follow-up time and larger sample size are required to validate our findings.