Investigation of Dynamic Culture on Matrix-derived Microcarriers as a Strategy to Modulate the Pro-Regenerative Phenotype of Human Adipose-derived Stromal Cells

Pre-conditioning of adipose-derived stromal cells (ASCs) by tuning the cellular microenvironment during expansion has the potential to modulate their pro-regenerative functionality. The current study investigated the effects of microcarrier composition (decellularized adipose tissue versus collagen), oxygen tension (2% versus ~20% O2) and stirring rate (static, 20, 40 rpm) on human ASCs cultured within spinner flask bioreactors. Dynamic culturing under 20% O2 resulted in more consistent cell growth on both microcarrier substrates, leading to increases in microcarrier contraction and stiffness. Culturing on the microcarriers modulated the hASC immunophenotype, with varying CD90 and CD26 expression levels observed under the different culture conditions. Interestingly, the gene expression levels of a range of pro-angiogenic and immunomodulatory factors were enhanced in the hASCs cultured on the collagen microcarriers at 20 rpm and 2% O2, supporting that the conditions within stirred bioreactors can be tuned to pre-condition hASCs for applications in vascular regeneration.