Adipose Tissue-Derived Microvascular Fragments Improve Vascularization, Lymphangiogenesis, and Integration of Dermal Skin Substitutes

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• 作者：Florian S. Frueh¹ ; ² ; ^{florian.frueh@uks.eu} ; Thomas Spä ; ter¹ ; Nicole Lindenblatt² ; Maurizio Calcagni² ; Pietro Giovanoli² ; Claudia Scheuer¹ ; Michael D. Menger¹ ; Matthias W. Laschke¹
• 关键词：ad-MVF ; adipose tissue-derived microvascular fragments ; FITC ; fluorescein isothiocyanate ; GFP ; green fluorescent protein ; LYVE-1 ; lymphatic vessel endothelial hyaluronan receptor-1 ; RBC ; red blood cell ; ROIs ; regions of interest ; STSG ; split-thickness skin grafts
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：137
• 期：1
• 页码：217-227
• 全文大小：5470 K
• 卷排序：137

文摘

Full-thickness skin defects can be covered with dermal skin substitutes in combination with split-thickness skin grafts. However, slow vascularization of the matrices bears the risk of wound infection and extends the length of hospitalization. To overcome these problems, we describe a promising vascularization strategy. Green fluorescent protein+ adipose tissue-derived microvascular fragments (ad-MVF) were isolated from epididymal fat pads of C57BL/6-Tg(CAG-EGFP)1Osb/J mice. ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects in the dorsal skinfold chamber of wild-type C57BL/6 mice. Nonseeded matrices served as controls. Vascularization, lymphangiogenesis, and integration of the implants were studied by using intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. ad-MVF rapidly reassembled into microvascular networks within the implants, which developed interconnections to the host microvasculature. Accordingly, vascularization of the implants was markedly accelerated, as indicated by a significantly higher microvessel density when compared with controls. Moreover, dense lymphatic networks originating from the green fluorescent protein+ ad-MVF developed within the implants. This was associated with an improved implant integration. Hence, seeding ad-MVF on collagen-glycosaminoglycan matrices represents a potential strategy to reduce morbidity and hospitalization of patients undergoing the treatment of full-thickness skin defects.