Single-Cell Gene Expression Analysis and Evaluation of the Therapeutic Function of Murine Adipose-Derived Stromal Cells (ASCs) from the Subcutaneous and Visceral Compartment

Abstract

Introduction. Adipose-derived stromal cells (ASCs) are a promising resource for wound healing and tissue regeneration because of their multipotent properties and cytokine secretion. ASCs are typically isolated from the subcutaneous fat compartment, but can also be obtained from visceral adipose tissue. The data on their equivalence diverges. The present study analyzes the cell-specific gene expression profiles and functional differences of ASCs derived from the subcutaneous (S-ASCs) and the visceral (V-ASCs) compartment. Material and Methods. Subcutaneous and visceral ASCs were obtained from mouse inguinal fat and omentum. The transcriptional profiles of the ASCs were compared on single-cell level. S-ASCs and V-ASCs were then compared in a murine wound healing model to evaluate their regenerative functionality. Results. On a single-cell level, S-ASCs and V-ASCs displayed distinct transcriptional profiles. Specifically, significant differences were detected in genes associated with neoangiogenesis and tissue remodeling (for example, Ccl2, Hif1α, Fgf7, and Igf). In addition, a different subpopulation ecology could be identified employing a cluster model. Nevertheless, both S-ASCs and V-ASCs induced accelerated healing rates and neoangiogenesis in a mouse wound healing model. Conclusion. With similar therapeutic potential in vivo, the significantly different gene expression patterns of ASCs from the subcutaneous and visceral compartments suggest different signaling pathways underlying their efficacy. This study clearly demonstrates that review of transcriptional results in vivo is advisable to confirm the tentative effect of cell therapies.