Comparison of Different Fabrication Techniques for Human Adipose Tissue Engineering in Severe Combined Immunodeficient Mice

Abstract

Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however, the long-term benefit depends on additional basic conditions that need further research.

The effect of medium selection on adipose-derived stem cell expansion and differentiation: implications for application in regenerative medicine

“…Maumus et al (2011) have considered how changes in adipose tissue microenvironment may participate in ADSC commitment and contribute to excessive adipose tissue development in obesity. Various studies have also shown that ADSC yield can vary depending on donor site (Du et al 2005;Katz et al 2005;Bunnell et al 2008;Maumus et al 2011;Frerich et al 2012). In our own studies using primary human tissue from other sources, such as skin, we have previously reported variation between tissues from different donors (Jubin et al 2011;Lenihan et al 2014), especially when analysed at the level of gene expression, and this may also explain the large amount of biological variation observed in the qRT-PCR results in this study.…”

“…In this study we isolated and cultured ADSCs in seven proliferation media as described by various authors (Katz et al 2005;Yoshimura et al 2006;Bunnell et al 2008;Du et al 2010;Zhou 2011;Aoyagi et al 2011;Frerich et al 2012) and two other proprietary media. Rate of proliferation is an important factor for clinical application, where autologous cells are required for reconstructive surgery.…”

Cultured meat from stem cells: Challenges and prospects

“…Due to an expanding world population and to increasing meat consumption in developing economies, it is predicted that meat consumption will double in the coming forty years (FAO, 2006). Although these predictions are associated with considerable uncertainty, the sheer magnitude of this alleged increase supports the assumption that demand will increase appreciably.…”

“…This is generally based on concerns about sustainability, environmental burden and animal welfare. These concerns have grown due to further intensification of livestock herding and slaughtering, and on the other hand a predicted rapid increase in global meat consumption (FAO, 2006).…”

Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes

“…For example, engineered constructs made of ASCs seeded on collagen microcarriers submitted to adipogenic differentiation and enriched or not in endothelial cells and fibrin matrix grafted to SCID mice featured a weight maintenance at 4 weeks in the range of 10% to 37% of the volume measured at day 12. 62 Another study has determined a a Error was calculated based on the standard deviation range of T 1g (the factor having by far the strongest incidence on the results of blood fraction calculated using Equation 6). …”