Adipose tissue engineering: state of the art, recent advances and innovative approaches

Abstract

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

Engineering of vascularized adipose constructs

“…Using a poly(lactide-co-gylcolide) scaffold and preadipocytes, adipose tissue was generated in vivo for the first time in 1999 (Patrick et al 1999). Since that time, researchers have mainly focused on three aspects of adipose tissue engineering: scaffolds for volume maintenance, matrices for supporting microenvironment and vascularization strategies (Tanzi and Fare 2009). Moreover, different precultivation and seeding strategies have been studied (Flynn et al 2000;Weiser et al 2008).…”

Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes

“…8,46 The tissue engineering approach we used in this study is based on cell sheet engineering that can be customized to produce adipose substitutes of different sizes and shapes that are easily manipulated and sutured. 35 In this model, cultured ASCs produce their own extracellular matrix elements, leading to cell sheets that are combined to form thicker human substitutes devoid of exogenous or synthetic biomaterials.…”

“…51,52 However, one should indeed compare DCE-MRI experiments with other measurements of blood perfusion/volume performed in AT but such data are scarce. Laser Doppler flowmeter, 133 Xe clearance, 103 Ru-labeled microspheres, and 46 Sc-labeled microspheres have been used to measure blood flow to brown AT. 53,54 A more recent study reported the use of molecules fluorescing in the nearinfrared region to assess blood perfusion in murine brown AT, demonstrating the possibility to perform noninvasive measurements of changes in blood flow and perfusion occurring in a given AT area.…”

Optimization of in vitro cultivation strategies for human adipocyte derived stem cells

“…Our aim was to study the effect of 2 different media with regard to their capacity to serve as a basic medium for preadipocytes before further differentiation into mature adipose tissue. One of the media used, BM 1, has been extensively described in the literature, 7,8,10 whereas the use of BM 2, which is the endothelial cell growth medium purchased from Promocell, has not yet been reported in preadipocyte cultivation protocols so far. By comparing both media before submitting the cells to identical culture conditions and differentiation schemes, we found a number of differences in the development of the 2 experimental groups.…”

“…1,2 In the literature, the tissue engineering of fat has been described with adipocyte derived stem cells (ADSCs), 3 which are the adipose-tissue-residing progenitor cells of adipocytes. [4][5][6][7] A cornerstone for the successful implantation of cells in vivo for preclinical investigations will certainly be the development of consistent strategies of cell cultivation and seeding on scaffolds, which might serve as a template for the desired 3-dimensional shape of the tissue to be engineered. Various preadipocyte and stem cell culture conditions and expansion methods have been developed, all attempting to improve the quality of tissue-engineered adipose tissue.…”