Background-Infantile hemangiomas (IHs) can cause significant morbidity during proliferation, yet there is no FDA-approved treatment. IHs are believed to form from stem cells (HemSCs), which differentiate towards an endothelial cell (HemECs) phenotype. Recently, propranolol has demonstrated effectiveness in the treatment of complicated IHs. We hypothesize that propranolol facilitates IH involution by altering cellular behavior in both HemECs and HemSCs.
Surgery duration is an independent predictor of complications, with a significantly increased risk above 3 hours. Although procedural complexity undoubtedly affects morbidity, operative time should factor into surgical decision making.
Botulinum toxin type A is a safe and effective method for treating focal hyperhidrosis, providing longer-lasting results than topical treatments without the necessity of invasive surgical procedures. Although more useful for axillary hyperhidrosis, botulinum toxin injections can also be effective in treating palmar and plantar disease. The effects of botulinum toxin last for six to nine months on average, and treatment is associated with a high satisfaction rate among patients. In this article, the authors discuss their preferred methods for treating axillary, palmar, and plantar hyperhidrosis. This article serves as guide for pretreatment evaluation, injection techniques, and posttreatment care.
Background
Infantile hemangiomas are the most common tumor of infancy, yet there are no FDA-approved therapeutics to date. Recently, the non-selective beta-adrenergic-blocker propranolol has been shown to be a safe and effective means of treating infantile hemangiomas, though its mechanism has yet to be elucidated. We have previously demonstrated that propranolol induces early and incomplete adipogenesis in stem cells derived from hemangiomas. We hypothesize that propranolol promotes dysregulated adipogenesis via the improper regulation of adipogenic genes.
Methods
Hemangioma stem cells isolated from resected infantile hemangioma specimens were treated with adipogenic medium for 1 or 4 days in either propranolol or vehicle. Cell death was measured by the incorporation of annexin V and propidium iodide by flow cytometry. Adipogenesis was assessed by visualizing lipid droplet formation by Oil Red O staining. Pro-adipogenic genes C/EBPβ, C/EBPβ, C/EBPδ, PPARδ, PPARγ, RXRα, and RXRγ were analyzed by quantitative reverse transcription and polymerase chain reaction.
Results
Hemangioma stem cells treated with propranolol increased lipid droplet formation compared to vehicle-treated cells indicating increased adipogenesis. Cell death as measured by FACS analysis indicated that the propranolol-treated cells died due to necrosis and not apoptosis. During adipogenesis, transcript levels of PPARδ, PPARγ, C/EBPβ, and C/EBPδ were significantly increased (p < 0.01) in propranolol-treated cells relative to control cells. In contrast, RXRα and RXRγ levels were significantly decreased (p < 0.05), and C/EBPα, a gene required for terminal adipocyte differentiation, was strongly suppressed by propranolol when compared to vehicle-treated cells (p < 0.01).
Conclusions
In hemangioma stem cells, propranolol accelerated dysregulated adipogenic differentiation characterized by improper adipogenic gene expression. Consistent with accelerated adipogenesis, propranolol significantly increased the expression of the pro-adipogenic genes, PPARγ , C/EBPβ and C/EBPγ compared to control. However, propranolol treatment also led to improper induction of PPARδ and suppression of C/EBPα, RXRα and RXRγ. Taken together this data indicates that propranolol promoted dysregulated adipogenesis and inhibited the hemangioma stem cells from becoming functional adipocytes, ultimately resulting in cell death. Understanding this mechanism behind propranolol's effectiveness will be a vital factor in producing more effective therapies in the future.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.