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

单细胞基因表达分析及对皮下和内脏小鼠脂肪来源的基质细胞 (ASC) 治疗功能的评估

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作者:Dominik Pförringer, Matthias M Aitzetmüller, Elizabeth A Brett, Khosrow S Houschyar, Richard Schäfer, Martijn van Griensven, Dominik Duscher

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.

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.

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.

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