Adipose tissue as a stem cell source for musculoskeletal regeneration

Abstract

Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells of stromal vascular fraction (SVF) cells. Subsequent adherent selection of the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs) capable of adipogenic, chondrogenic, myogenic, and osteogenic differentiation in vitro on scaffolds in bioreactors and in vivo in pre-clinical animal models. Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead release immunosuppressive factors, such as prostaglandin E2. These immunomodulatory features suggest that allogeneic and autologous ASCs will engraft successfully for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can be used to direct differentiation of ASCs to particular lineages. We discuss the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells.

Figure 1. Tissue Engineering approach

ASCs are combined with scaffolds and bioreactors that act in tandem to provide developmental cues to undifferentiated ASCs, to result in a 3D engineered construct with functional properties.

Figure 2. Engineering bone from ASCs

(A) Schematic of bioreactor design (taken from (123) and reproduced with permission from Liebert Inc.) (B, C) Trichrome stains and osteopontin immunohistochemical stains for constructs cultured under static (B) and perfused (C) conditions. Matrix and cell distribution are greatly improved in perfused constructs. (D) μCT (left) and SEM images (middle and right) of bone constructs cultured with ASCs in perfusion bioreactors. SEMs show alignment of matrix with mineral deposits. (Images modified from (55) and reproduced with permission from Liebert Inc.)