Effects of Modulating the Culture Microenvironment on the Growth and Secretome of Human Adipose-Derived Stromal Cells

Zhiyu Liang, The University of Western Ontario

Abstract

The cell microenvironment plays a critical role in modulating adipose-derived stromal cell (ASC) proliferation and paracrine function. The current study investigated the effects of decellularized adipose tissue (DAT) coatings, low-level oscillatory shear stress (~0.04‑0.3 dyn/cm²), hypoxia (2% O₂), and pro-inflammatory cytokine priming with IFN-g and TNF-a on human ASC proliferation and paracrine factor secretion in the context of a rocking bioreactor. Culturing under 20% O₂ resulted in a higher cell density after 7 days of culture. Without cytokine priming, the varying culture conditions significantly impacted the levels of the pro-angiogenic factors VEGF, HGF, and angiogenin detected in conditioned media samples. In contrast, when the cells were primed, the levels of the immunomodulatory factors IL-6 and IL-8 were most affected by the varying microenvironmental factors. Overall, a novel bioreactor system was developed for ASC expansion and preconditioning, demonstrating that the cell microenvironment could be tuned to modulate ASC paracrine factor secretion.