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Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells.

ABSTRACT: Propranolol has been widely used in treating infantile hemangiomas (IHs). But recurrence of IHs was found in some cases on cessation of propranolol treatment. The other is that Chinese individuals reacted to propranolol differently from American Whites. Whether the difference of sensitivity is due to the ? adrenoceptor (?-AR) expression pattern of hemangioma initiating cells remains unclear. In the present study, we isolated hemangioma-derived stem cells (hemSCs) from proliferative IHs and analyzed the biological characteristics and ?-AR expression pattern of hemSCs by immunostaining, Western blotting and multilineage differentiation assay as well. We also tested the effects of propranolol on hemSCs by evaluating VEGF expression, proliferation and apoptosis related parameters. Our results indicated that CD133(+) hemSCs located pre-vascular in proiferative IH tissues. Both ?1 and ?2-AR were expressed, while ?2-AR was dominant on hemSCs. Propranolol at 100-150 ?M inhibited proliferation of hemSCs, not did 50 ?M. Propranolol down-regulated VEGF expression of hemSCs, instead of inducing apoptosis. The adipogenic potential was enhanced by propranolol. Therefore, our current results suggested propranolol could not induce apoptosis of hemSCs, but played a curative role though suppressing VEGF synthesis and enhancement of adipogenesis of hemSCs. Our results might partially provide the insight of mechanism of relapse in some cases on cessation of propranolol treatment.

SUBMITTER: Ma X

PROVIDER: S-EPMC4128992 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells.

Ma Xiaorong X Zhao Tinghui T Ouyang Tianxiang T Xin Shujia S Ma Yueting Y Chang Mengling M

International journal of clinical and experimental pathology 20140615 7

Propranolol has been widely used in treating infantile hemangiomas (IHs). But recurrence of IHs was found in some cases on cessation of propranolol treatment. The other is that Chinese individuals reacted to propranolol differently from American Whites. Whether the difference of sensitivity is due to the β adrenoceptor (β-AR) expression pattern of hemangioma initiating cells remains unclear. In the present study, we isolated hemangioma-derived stem cells (hemSCs) from proliferative IHs and analy ...[more]

PMID: 25120757

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Project description:BackgroundHuman bone marrow-derived mesenchymal stem cells (hBMSCs) can differentiate into adipocytes upon stimulation and are considered an appropriate cell source for adipose tissue engineering. In addition to biochemical cues, the stiffness of a substrate that cells attach to has also been shown to affect hBMSC differentiation potential. Of note, most current studies are conducted on monolayer cultures which do not directly inform adipose tissue engineering, where 3-dimensional (3D) scaffolds are often used to create proper tissue architecture. In this study, we aim to examine the adipogenic differentiation of hBMSCs within soft or stiff scaffolds and investigate the molecular mechanism mediating the response of hBMSCs to substrate stiffness in 3D culture, specifically the involvement of the integral membrane protein, caveolin-1 (CAV1), known to regulate signaling in MSCs via compartmentalizing and concentrating signaling molecules.MethodsBy adjusting the photo-illumination time, photocrosslinkable gelatin scaffolds with the same polymer concentration but different stiffnesses were created. hBMSCs were seeded within soft and stiff scaffolds, and their response to adipogenic induction under different substrate mechanical conditions was characterized. The functional involvement of CAV1 was assessed by suppressing its expression level using CAV1-specific siRNA.ResultsThe soft and stiff scaffolds used in this study had a compressive modulus of ~0.5 kPa and ~23.5 kPa, respectively. hBMSCs showed high viability in both scaffold types, but only spread out in the soft scaffolds. hBMSCs cultured in soft scaffolds displayed significantly higher adipogenesis, as revealed by histology, qRT-PCR, and immunostaining. Interestingly, a lower CAV1 level was observed in hBMSCs in the soft scaffolds, concomitantly accompanied by increased levels of Yes-associated protein (YAP) and decreased YAP phosphorylation, when compared to cells seeded in the stiff scaffolds. Interestingly, reducing CAV1 expression with siRNA was shown to further enhance hBMSC adipogenesis, which may function through activation of the YAP signaling pathway.ConclusionsSoft biomaterials support superior adipogenesis of encapsulated hBMSCs in 3D culture, which is partially mediated by the CAV1-YAP axis. Suppressing CAV1 expression levels represents a robust method in the promotion of hBMSC adipogenesis.

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Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells.

Publications

Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells.

Similar Datasets

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