Adipose Tissue Engineering Based on Mesenchymal Stem Cells and Basic Fibroblast Growth Factorin Vitro

Abstract

Despite the clinical need for reconstructive and plastic surgery, the supply of engineered adipose tissue equivalents still remains a challenge. As yet, only preadipocytes have been applied as a cell material for the in vitro tissue engineering of fat. Herein, we report the establishment of a three-dimensional (3-D) long-term cell culture, using bone marrow-derived mesenchymal stem cells (MSCs) as an alternative cell source and custom-made poly(lactic-co-glycolic acid) (PLGA) scaffolds as a cell carrier. Cell-polymer constructs were cultivated for 4 weeks in both the absence and presence of basic fibroblast growth factor (bFGF), which was previously shown to strongly enhance the adipogenesis of MSCs in conventional 2-D short-term culture. A striking enhancement of the adipogenic differentiation of MSCs and tissue development caused by bFGF in the 3-D culture was observed by osmium tetroxide histology and scanning electron microscopy. At the molecular level, reflecting the increased accumulation of lipids, bFGF increased the enzymatic activity of glycerol-3-phosphate dehydrogenase, a late marker of adipogenesis, and the expression of adipocyte-specific genes peroxisome proliferator activated receptor-gamma2 (PPARgamma2) and glucose transporter-4 (GLUT4), as assessed by reverse transcription-polymerase chain reaction. This study demonstrates that the use of bone marrow-derived MSCs, especially in combination with bFGF, may represent a promising approach to adipose tissue engineering.

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

“…However, as found for BM MSCs and some committed preadipocyte lines (132)(133)(134), this requires the ASCs to be seeded onto polymeric three-dimensional (3-D) scaffolds after adipogenic induction in vitro (129)(130)(131). Moreover, at least one study suggests that donor ASCs may contribute to adipose tissue regeneration by stimulating differentiation of host-derived adipocytes ( 131 ).…”

Surface modified cellulose scaffolds for tissue engineering

“…PLGA is a biocompatible, polyester copolymer of lactic and glycolic acids, which degrades in vivo. Due to its tuneable mechanical properties, it has been used to prepare biodegradable scaffolds for a range of applications including: bone grafts (Agrawal et al 2014a, b, c); to generate adipose tissue for reconstructive surgery (Neubauer et al 2005); and spun into fibres for seeding cells (Teng et al 2002). However, when PLGA degrades in vivo, the acidic metabolites can have a detrimental effect on the local pH of the extracellular matrix (ECM), which can cause inflammation and an immune response, or even cell and tissue necrosis (Willerth and Sakiyama-Elbert 2008;Liu et al 2006).…”

Engineering adipose-like tissue in vitro and in vivo utilizing human bone marrow and adipose-derived mesenchymal stem cells with silk fibroin 3D scaffolds

“…For these cellbased applications, human mesenchymal stem cells derived from bone marrow (hMSCs) or human adipose tissue (hASCs) have both been suggested as potential cell sources for adipose repair therapies [13][14][15][16]. hMSCs and hASCs are readily isolatable from bone marrow aspirates or adipose stromal vascular fractions, respectively, and can differentiate into a variety of mesenchymal lineages.…”

“…hMSCs and hASCs are readily isolatable from bone marrow aspirates or adipose stromal vascular fractions, respectively, and can differentiate into a variety of mesenchymal lineages. Both these properties are desirable attributes for incorporation into clinical repair modalities [13,14,16]. Currently, however the efficacy of exogenously-delivered stem cell populations to support the generation of long-term volume stable adipose tissue in vivo is limited by suboptimal properties of their biomaterial carriers including insufficient biocompatibility and rapid scaffold degradation rates [15,16].…”