Role of mesenchymal stem cell-derived soluble factors and folic acid in wound healing

Abstract

Introduction Wound healing is an important and complicated process that involves cell proliferation, migration, angiogenesis, reepithelization, and tissue remodeling as a result of complex interactions between growth factors, extracellular matrix molecules, and cells [1]. Stem cells have emerged as a promising treatment for wounds due to their ability to renew and differentiate themselves. Adult stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ASCs) are not hard to obtain due to ethical concerns and availability like embryonic stem cells. BMSCs and ASCs can be easily isolated in adults [2,3]. Mesenchymal stem cells (MSCs), a heterogeneous subset of stromal stem cells, are multipotent adult stem cells that are present in multiple tissues, including the umbilical cord, bone marrow, and fat tissue. They are reproducible and have a high potential for use in different areas [4]. Because of their stromal origin, they are supportive and durable. MSCs have the potential to differentiate into different cell types primarily in connective tissue when provided with appropriate microenvironmental conditions [5]. They have osteogenic, adipogenic, chondrogenic, and myogenic differentiation capacities in in vitro conditions Background/aim: Mesenchymal stem cells (MSCs) are a type of adult stem cell consisting of a heterogeneous subset of stromal stem cells that can be isolated from adult tissues. Folic acid is another important contributor to tissue regeneration and repair, which affects the synthesis of some building block molecules used for wound healing. In this study, we examine the effect of folic acid and MSCderived soluble factors in the wound healing model. Materials and methods: Human umbilical vein endothelial cells (HUVECs) and bone marrow-derived MSCs (BMSCs) were cultured for this study. Cell proliferation analysis was done with xCELLigence RTCA. After 48 h of cultivation, the cell culture medium was collected as MSC conditional medium containing mesenchymal stem cell-derived soluble factors (MDFs). Different concentrations of MDFs (12%, 25%, 50%, 75%, and 100%) were applied to the HUVEC cell line. Folic acid (25, 30, 50, 60, 75, 90, and 100 µM) was tested by application of three different groups (control, 25 µM folic acid, 625 µM folic acid inhibitors) for proliferation on the HUVEC cell line. The combined effects of folic acid and MDFs were tested on the HUVEC cell line with 25 µM folic acid and 50 µM MDFs. All data were statistically analyzed using SPSS 15.0 for Windows. Results: Significant differences were observed between controls and cells treated with folic acid, as well as between controls and both folic acid and MDFs (P < 0.05). Among the treated groups, the fastest wound closure rate was seen in cells treated with both folic acid and MDFs. Conclusion: The results show that both folic acid and MDFs increased the wound healing rate in HUVECs when they were used separately. The strongest benefits were seen in treatment using folic acid and MDFs...

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