Adipose Tissue-Derived Microvascular Fragments From Male and Female Fat Donors Exhibit a Comparable Vascularization Capacity.

Ann-Sophie Mai,Julia E Marschall,Ruth M Nickels,Wolfgang Metzger,Lea K Brücker,Matthias W Laschke,Michael D Menger,Thomas Später

doi:10.3389/fbioe.2021.777687

Ann-Sophie Mai, Julia E Marschall + Show 6 more

Open Access

https://doi.org/10.3389/fbioe.2021.777687

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Abstract

Adipose tissue-derived microvascular fragments (MVF) represent effective vascularization units for tissue engineering. Most experimental studies exclusively use epididymal fat tissue of male donor mice as a source for MVF isolation. However, in future clinical practice, MVF-based approaches may be applied in both male and female patients. Therefore, we herein compared the vascularization capacity of MVF isolated from the epididymal and peri-ovarian fat tissue of male and female donor mice. Freshly isolated MVF from male and female donors did not differ in their number, length distribution, viability and cellular composition. After their assembly into spheroids, they also exhibited a comparable in vitro sprouting activity. Moreover, they could be seeded onto collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects within mouse dorsal skinfold chambers. Repetitive intravital fluorescence microscopy as well as histological and immunohistochemical analyses revealed a comparable vascularization and incorporation of implants seeded with MVF of male and female origin. Taken together, these findings demonstrate that the vascularization capacity of MVF is not gender-specific.

Highlights

In tissue engineering, the function and survival of implanted tissue constructs crucially depends on their rapid and adequate vascularization, which ensures a sufficient oxygen and nutrient supply (Rouwkema and Khademhosseini, 2016)
Gender Specificity of Microvascular Fragments tempting to speculate that microvascular fragments (MVF) isolated from adipose tissue of male and female donors may markedly differ in terms of their angiogenic potential and in vivo vascularization capacity
MVF exhibit a high angiogenic activity after their isolation from adipose tissue (Frueh et al, 2017a; Frueh et al, 2017b; Laschke et al, 2021). These fully functional vessel segments are commonly used in angiogenesis research to focus on basic mechanisms of microvascular network formation and the interaction of newly developing microvessels with the extracellular matrix in controlled three-dimensional environments (Kirkpatrick et al, 2007; Edgar et al, 2014; Utzinger et al, 2015)

Summary

Introduction

The function and survival of implanted tissue constructs crucially depends on their rapid and adequate vascularization, which ensures a sufficient oxygen and nutrient supply (Rouwkema and Khademhosseini, 2016). MVF represent a randomized mixture of functional arteriolar, capillary and venular vessel segments, which can be isolated in large amounts from adipose tissue by means of mechanical dissection and enzymatic digestion (Frueh et al, 2017a; Später et al, 2017a; Frueh et al, 2017b) After their isolation, MVF exhibit an intact vessel morphology with a central lumen surrounded by endothelial cells and stabilizing pericytes (Laschke and Menger, 2015). Gender Specificity of Microvascular Fragments tempting to speculate that MVF isolated from adipose tissue of male and female donors may markedly differ in terms of their angiogenic potential and in vivo vascularization capacity. Freshly isolated MVF of male and female origin were seeded onto collagenglycosaminoglycan (CGAG) matrices, which were subsequently implanted into full-thickness skin defects within mouse dorsal skinfold chambers to analyze their vascularization and incorporation by means of intravital fluorescence microscopy, histology and immunohistochemistry throughout an observation period of 2 weeks

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