Wound healing potential of human umbilical cord mesenchymal stem cell conditioned medium: An in vitro and in vivo study in diabetes-induced rats

Abstract

Background and Aim: Human umbilical cord mesenchymal stem cells (hUC-MSCs) and its conditioned medium (CM) promote wound healing. This study investigated the wound healing potential of hUC-MSC CM in vitro and in vivo using diabetic animal models. Materials and Methods: The CM from hUC-MSC CM prepared under hypoxic conditions (hypoxic hUC-MSC) was evaluated for stimulating rat fibroblast growth, collagen production (in vitro), and wound healing in animal models (in vivo). An excision wound on the dorsal side of the diabetes-induced rats was established, and the rats were randomly divided into non-treatment, antibiotic, and hypoxic hUC-MSC CM groups. The cell number of fibroblasts and collagen secretion was evaluated and compared among the groups in an in vitro study. By contrast, wound size reduction, width of re-epithelialization, and the collagen formation area were assessed and compared among the groups in an in vivo study. Results: CM under hypoxic conditions contained a higher concentration of wound healing-related growth factors. Hypoxic hUC-MSC CM could facilitate fibroblast cell growth and collagen synthesis, although not significant compared with the control group. Re-epithelialization and collagen production were higher in the hUC-MSC CM group than in the antibiotic and non-treatment groups. Conclusion: Hypoxic hUC-MSC CM possessed more positive effects on the wound healing process based on re-epithelialization and collagen formation than antibiotic treatment did.

Fibroblast matrix implants—a better alternative for incisional hernia repair?

“…bFGF, known as fibrogenic cytokines, may trigger the proliferation of fibroblast and stimulate the production of connective tissue, which ultimately leads to fibrous and capillary growth [40][41][42]. The increase in fibroblast cell number and collagen synthesis in our preliminary in vitro investigation as well as other investigations in our laboratory [20] show that the CM hUC-MSC supports fibroblast cell growth, although the number of FMI scaffolds was small. Even though, the ELISA could not distinguish whether the collagen was produced by the fibroblasts or released from the collagen-coated scaffold, our result showed that the CM-treated group had significantly higher collagen concentration.…”

“…Normally, the immature type III collagen is converted into the more mature type I collagen. However, this process is delayed in the presence of foreign bodies such as synthetic mesh prostheses or biomaterial prostheses [20]. It leads to an increased deposition of type III collagen, which results in significantly reduced mechanical stability and strength of the local tissue [22].…”

“…It contains various growth factors, e.g. vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), that promote the wound healing process [20,38,39]. bFGF, known as fibrogenic cytokines, may trigger the proliferation of fibroblast and stimulate the production of connective tissue, which ultimately leads to fibrous and capillary growth [40][41][42].…”

“…Fibroblasts are responsible for collagen synthesis and the process of wound healing [3]. CM hUC-MSCs containing soluble growth factors and inflammatory mediators are known to promote wound healing by accelerating cell migration, and they may facilitate collagen synthesis [3,19,20].…”

Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications

“…In vivo, re‐epithelialization and collagen production were increased using hUC‐MSC‐CM. [ 150 ] MSC‐CM applications seem promising for wound healing models. However, as an alternative to systemic application, which is the predominant route of administration in the literature, it is thought that topical applications or the development of a CM‐containing patch may be beneficial for accelerating wound healing.…”