The transdifferentiation of human dedifferentiated fat cells into fibroblasts: An in vitro experimental pilot study

Abstract

Background: Skin grafting is a common method of treating damaged skin; however, surgical complications may arise in patients with poor health. Currently, no effective conservative treatment is available for extensive skin loss. Mature adipocytes, which constitute a substantial portion of adipose tissue, have recently emerged as a potential source of stemness. When de-lipidated, these cells exhibit fibroblast-like characteristics and the ability to redifferentiate, offering homogeneity and research utility as “dedifferentiated fat cells.” Methods and results: We conducted an in vitro study to induce fibroblast-like traits in the adipose tissue by transdifferentiating mature adipocytes for skin regeneration. Human subcutaneous fat tissues were isolated and purified from mature adipocytes that underwent a transformation process over 14 days of cultivation. Microscopic analysis revealed lipid degradation over time, ultimately transforming cells into fibroblast-like forms. Flow cytometry was used to verify their characteristics, highlighting markers such as CD90 and CD105 (mesenchymal stem cell markers) and CD56 and CD106 (for detecting fibroblast characteristics). Administering dedifferentiated fat cells with transforming growth factor-β at the identified optimal differentiation concentration of 5 ng/mL for a span of 14 days led to heightened expression of alpha smooth muscle actin and fibronectin, as evidenced by RNA and protein analysis. Meanwhile, functional validation through cell sorting demonstrated limited fibroblast marker expression in both treated and untreated cells after transdifferentiation by transforming growth factor-β. Conclusion: Although challenges remain in achieving more effective transformation and definitive fibroblast differentiation, our trial could pave the way for a novel skin regeneration treatment strategy.