BackgroundThe use of stem cells from adipose tissue or adipose-derived stem cells (ASCs) in regenerative medicine could be an interesting alternative to bone marrow stem cells because they are easily accessible and available in large quantities. The aim of this study was to evaluate the potential effect of ASCs on the healing of 12 mm diameter-excisional wounds (around 110 mm2) in nude mice.MethodsThirty nude mice underwent surgery to create one 12-mm excisional wound per mouse (spontaneous healing, n = 6; Cytocare® 532, n = 12; ASCs, n = 12). The Galiano wound model was chosen to avoid shrinkage and thus slow the spontaneous healing (SH) of mouse skin, making it closer to the physiology of human skin healing. Transparent dressings were used to enable daily healing time measurements to be taken. Immunohistochemistry, histological and blood perfusion analysis were carried out on the healed skin.ResultsThe in vivo results showed the effectiveness of using ASCs on reducing the time needed for complete healing to 21.2 days for SH, 17.4 days for vehicle alone (Cytocare® 532) and 14.6 days with the addition of ASCs (p < 0.001). Moreover, cutaneous perfusion of the healed wound was significantly improved in ASC-treated mice compared to SH group, as shown by laser Doppler flowmetry and the quantitation of blood vessels using immunohistochemistry of αsmooth muscle actin.ConclusionsThe tolerance and efficacy of cryopreserved ASCs to accelerate the complete closure of the wound by increasing the maturation of the skin and its blood perfusion, shows their therapeutic benefit in the wound healing context.

Diabetic foot ulcer (DFU) is a problem worldwide, and prevention is crucial. We hypothesized that the inability of the skin to respond to pressure is involved in DFU pathogenesis and could be an important predictive factor to take into account. We included 29 patients with DFU and 30 patients with type 2 diabetes without DFU. Neuropathy and skin blood flow at rest were assessed in response to acetylcholine, sodium nitroprusside, local heating (42°C), and to nonnoxious locally applied pressure. Results were compared with those obtained from 10 healthy age-matched control subjects. Vasodilatation in response to pressure was significantly impaired in both groups with diabetes compared with healthy subjects. The vasodilator capacity to pressure was significantly lower in patients with DFU compared with those without DFU, despite the absence of significant difference in cutaneous pressure perception threshold and vascular reactivity to acetylcholine, sodium nitroprusside, and heat. This pronounced alteration of neurovascular response to pressure in patients with DFU is a good marker of skin vulnerability and could be used to better predict individuals at risk.

Sensing environmental temperature is a key factor allowing individuals to maintain thermal homeostasis via thermoregulatory mechanisms, including changes to skin blood flow. Among transient receptor potential channels, transient receptor potential vanilloid 3 (TRPV3) is a heat-activated cation channel highly expressed in keratinocytes. However, the role of TRPV3 in triggering heat-evoked cutaneous vasodilation is unknown. Using a murine in vivo model of local acute environmental heat exposure in the skin, we show that TRPV3 is involved in the local thermoregulatory control of skin blood flow by initiating the release of calcitonin gene-related peptide and nitric oxide in response to local heating of the skin. In addition to their contribution in local heat-evoked vasodilation, TRPV3, calcitonin gene-related peptide, and nitric oxide also contribute to internal body temperature stability during passive whole-body heating. This study provides in vivo demonstration of the role of TRPV3 as a strong modulator of cutaneous vascular thermoregulatory mechanisms.