Impact of neoadjuvant chemotherapy on the functionality of adipose-derived mesenchymal stromal cells and their modulatory effects on fibroblasts in oncology patients

Adipose-derived mesenchymal stromal cells (AD-MSCs), also known as mesenchymal stem cells, hold great promise in regenerative medicine due to their pleiotropic effects, including the secretion of cytokines, chemokines, and growth factors. These cells can promote tissue repair, enhance angiogenesis, and modulate inflammation. However, understanding neoadjuvant chemotherapy’s impacts on AD-MSC functionality, immunophenotype, cytokine secretion, and their interactions with fibroblasts remains insufficient. This study aimed to investigate the effects of chemotherapy on AD-MSCs and their ability to influence fibroblast function in vitro. Human, autologous AD-MSCs and skin fibroblasts were isolated from two patient cohorts - those without and those after neoadjuvant chemotherapy, from subcutaneous adipose tissue obtained during surgical procedures. AD-MSCs identity was confirmed by flow cytometry, positive and negative markers, and by induction of adipogenic, osteogenic, and chondrogenic differentiation. Autologous fibroblasts were co-cultured with AD-MSCs to assess fibroblast chemotaxis, proliferation, migration, cytokine secretion, cell-cycle distribution, collagen deposition, and gene expression. Flow cytometric analysis of surface markers, secreted cytokines, transcriptomic analysis, and the cell cycle revealed no significant differences between AD-MSCs from patients who either received or did not receive chemotherapy. A slight increase in mitochondrial activity was observed in cells from chemotherapy-treated patients. Analysis of dermal fibroblasts revealed significant alterations in their biological activity post-chemotherapy. Their chemotactic activity, migration, and collagen production were weakened, and their cytokine secretion profile was altered. Co-culture of autologous fibroblasts and AD-MSCs showed that AD-MSCs stimulated fibroblast chemotactic activity in both groups. However, AD-MSCs stimulated fibroblast migration and proliferation only in patients without previous chemotherapy. This study shows that AD-MSCs maintain their functionality after chemotherapy and can influence fibroblast activity. These findings add to understanding the chemotherapy effects on skin fibroblasts and AD-MSCs and support further research to optimize the use of AD-MSCs in regenerative medicine for oncology patients, particularly in wound healing and tissue repair post-cancer treatments.