Abstract
Microenvironmental factors can modulate the cellular status of adipose tissue-derived stem cells (ASCs). In response to microenvironmental changes, cells can remodel extracellular matrix (ECM) proteins, which play an important role in regulating cell behaviors. During adipogenic differentiation, ECM components secreted from ASCs remodel dramatically. To evaluate the role of stepwise adipogenesis-induced cellular secretion of ECM on the behavior of ASCs, we cultured ASCs in growth and adipogenic media, and ECM secreted from cells was characterized and decellularized. The ASCs were then reseeded on decellularized ECM (d-ECM) to determine the regulatory effects of ECM on cellular behaviors. During adipogenesis, cell-secreted ECM underwent remodeling characterized by conversion from fibronectin-rich ECM to laminin-rich ECM. The cellular status of ASCs was tested after reseeding on decellularized ECM. When reseeded on growth d-ECM, ASCs exhibited greater migration ability. In contrast, ASCs seeded on adipogenic d-ECM underwent adipogenic differentiation. In addition, integrin subunit αv and integrins α6 and α7 were detected at significantly greater levels in ASCs cultured on growth and adipogenic d-ECM, respectively, suggesting that integrins play an important role in ASC migration and adipogenesis. This study demonstrated that stepwise adipogenesis-induced ECM production plays an important role in ASC migration and differentiation. In addition, this study provided a strategy to achieve precise regulation of stem cell function in adipose tissue engineering.
Highlights
Adipose tissue-derived stem cells (ASCs) originate from a wide range of sources and exhibit multilineage differentiation ability [1]
Lipid droplets were visually observed in ASCs cultured in adipogenesis medium (AD) for 14 days, and no lipid droplets were observed in ASCs cultured in growth medium (GM) (Fig. S1)
Laminin increased gradually during adipogenic differentiation but was only present at low levels in the extracellular matrix (ECM) produced by undifferentiated ASCs (Figure 1)
Summary
Adipose tissue-derived stem cells (ASCs) originate from a wide range of sources and exhibit multilineage differentiation ability [1]. In plastic and reconstructive surgery, ASCs are beneficial for stem cell therapy and adipose tissue regeneration. In these processes, the use of a combination of biomaterials and adipose-derived stem cell transplantation results in better outcomes [2, 3]. To modify the surfaces of biomaterials to allow for the regulation of cellular behaviors, it is important to fully understand the environment in which cells are grown in vivo. ASCs are found within the stem cell niche, a specialized microenvironment that supports cellular homeostasis [4]. ASCs are regulated by cell ECM signaling. Previous studies have shown that self-renewal and differentiation of ASCs are tightly regulated by ECM organization and composition [6]
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