TY  - JOUR
A1  - Strohmeier, Karin
A1  - Hofmann, Martina
A1  - Jacak, Jaroslaw
A1  - Narzt, Marie-Sophie
A1  - Wahlmueller, Marlene
A1  - Mairhofer, Mario
A1  - Schädl, Barbara
A1  - Holnthoner, Wolfgang
A1  - Barsch, Martin
A1  - Sandhofer, Matthias
A1  - Wolbank, Susanne
A1  - Priglinger, Eleni
T1  - Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema
JF  - Biomedicines
N2  - Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.
KW  - Tissue Engineering
KW  - Adipose Tissue
KW  - Lipedema
KW  - Endothelial Cells
Y1  - 
VL  - 2022
IS  - 10(5)
SP  - 1163
ER  - 
TY  - JOUR
A1  - Hromada, Carina
A1  - Hartmann, Jaana
A1  - Oesterreicher, Johannes
A1  - Stoiber, Anton
A1  - Daerr, Anna
A1  - Schädl, Barbara
A1  - Priglinger, Eleni
A1  - Teuschl-Woller, Andreas H.
A1  - Holnthoner, Wolfgang
A1  - Heinzel, Johannes Christoph
A1  - Hercher, David
T1  - Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-Induced Apoptosis of Lymphatic Endothelial Cells In Vitro
JF  - Biomolecules
N2  - Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types' migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC-LEC interaction.
KW  - Tissue Engineering
KW  - peripheral nerve regeneration
KW  - lymphangiogenesis
KW  - Schwann cells
KW  - lymphatic endothelial cells
Y1  - 
VL  - 2022
IS  - 12, 6
SP  - 820
ER  -