Fibroblast-Adipocyte Lineage Cell Interactions Result in Differential Production of Extracellular Matrix Proteins.

INTRODUCTION: Scarring from traumatic injury, burns, and other complications remains a significant problem that diminishes quality of life for millions of people worldwide. A common target for the development of new therapies to promote healing and reduce scarring are myofibroblasts because of their central role in pathological scarring. Recent work indicates that adipocyte lineage cells also contribute to the wound healing process, including clinical reports that indicate that the placement of autologous adipose micrografts at the surgical site improves the appearance and pliability of existing scars. METHODS: To better understand how adipocyte lineage cells interact with fibroblasts to promote healing, we first utilized an in vitro model of wound healing to visualize fibroblast spheroid collagen deposition via time-lapse imaging. We then introduced pre-adipocyte and adipocyte spheroids to visualize pair-wise spheroid interactions and collagen deposition among all three cell types. Finally, we quantified differences in the extracellular matrix (ECM) proteins produced using liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: We found that all three cell-types contribute to ECM deposition and that the composition of the ECM proteins, or matrisome, was significantly different depending on which cells were co-cultured together. CONCLUSIONS: By better understanding the interactions among these cell types, novel adipose-tissue-based therapeutic approaches can be developed to improve wound healing and reduce scar tissue. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-024-00829-8.