Acute and chronic wound fluids inversely influence adipose‐derived stem cell function: molecular insights into impaired wound healing

Abstract

Wound healing is a complex biological process that requires a well-orchestrated interaction of mediators as well as resident and infiltrating cells. In this context, mesenchymal stem cells play a crucial role as they are attracted to the wound site and influence tissue regeneration by various mechanisms. In chronic wounds, these processes are disturbed. In a comparative approach, adipose-derived stem cells (ASC) were treated with acute and chronic wound fluids (AWF and CWF, respectively). Proliferation and migration were investigated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and transwell migration assay. Gene expression changes were analysed using quantitative real time-polymerase chain reaction. AWF had a significantly stronger chemotactic impact on ASC than CWF (77·5% versus 59·8% migrated cells). While proliferation was stimulated by AWF up to 136·3%, CWF had a negative effect on proliferation over time (80·3%). Expression of b-FGF, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was strongly induced by CWF compared with a mild induction by AWF. These results give an insight into impaired ASC function in chronic wounds. The detected effect of CWF on proliferation and migration of ASC might be one reason for an insufficient healing process in chronic wounds.

Moist exposed burn ointment promotes cutaneous excisional wound healing in rats involving VEGF and bFGF

“…Decreased levels of VEGF and/or bFGF, or inhibition of their activity leads to the limited migration of fibroblasts and the delay of wound healing (20,44). In the present study, rb-bFGF enhanced the protein and gene expression of VEGF and bFGF, which is similar to the results of a previous study (45). It is well known that the expression of VEGF and bFGF is increased following skin injury, particularly in the early stage of healing.…”

“…It is well known that the expression of VEGF and bFGF is increased following skin injury, particularly in the early stage of healing. A previous report showed that the acute wound fluid, which is rich in VEGF and bFGF, increases the mRNA levels of VEGF and bFGF (45). Since a similar effect between MEBO and rb-bFGF in treating cutaneous excisional wounds was observed, it was concluded that MEBO promotes wound healing by increasing VEGF and bFGF production.…”

Role of adipose‐derived stem cells in wound healing

“…The ability of ASCs to proliferate and migrate was significantly hampered when treated with CWF that could lead to impaired regenerative potential of ASCs. However, the expression of growth factors (VEGF, bFGF, and MMP9) was strongly induced in CWF‐treated cells as opposed to AWF‐treated ASCs . Therefore, the use of ASC for wound healing should be considered carefully, as well as delivery methods and dosing regimen as the use of stem cells may differ depending on the wound type.…”

Trauma and Stem Cells: Biology and Potential Therapeutic Implications

“…In vitro migration assays on ADSC found that acute wound fluid was more chemoattractant than chronic wound fluid. Acute wound fluid has been shown to encourage ADSC proliferation while chronic wound fluid suppressed proliferation [37]. This suggests a growth factor or cytokine imbalance that impairs proper healing in chronic wounds.…”