Autologous administration of adipose stromal cells improves skin flap survival through neovascularization: An experimental study

Abstract

One of the most severe complications in aesthetic and reconstructive surgeries is the partial or total necrosis of a skin flap. In our experimental study, we demonstrated the use of adipose‐derived stem cells in the increase of skin flap survival rates. Stem cells were isolated from the fat of Wistar rats and genetically modified to permanently produce a green fluorescent protein (GFP). Two random‐pattern skin flaps (2 cm × 8 cm) were elevated on the dorsal area of the spine, and after being separated from the surgical wounds with a thin silicone sheet, they were placed back onto their original location. Then, the autologous GFP‐producing cells were injected intradermally into the dorsal area of the rats. At the seventh day, after the implantation of the stem cells, a clinical and immunohistochemical control was performed. The fluorescence microscopy revealed green vascular formations, suggesting that autologous GFP stromal cells were converted into endothelial cells through neovascularization. In the control skin flaps, where no stromal cells were used, no fluorescence was observed. The statistical analysis showed significantly lower necrosis rates in the right‐sided flaps (i.e., the flaps where adipose‐derived stromal cells were injected) compared with the left‐sided ones. Findings from our study demonstrate that adipose‐derived stem cells play an important role in the improvement of skin flap survival. Neovascularization is an effective way of achieving it.

Superiority of Adipose-derived CD34+ Cells over Adipose-derived Stem Cells in Promoting Ischamic Tissue Survival

“…It has been reported that newly isolated ADSC express CD34. After culture, ADSC lose the marker CD34 [28] . Moreover, CD34+ cells in adipose tissue contain M2 macrophage subpopulations that express IL-10 and other immunoregulatory genes.…”

A clinical perspective on adipose‐derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery

“…The success of Lu and colleagues was replicated by Suartz in 2014, who showed that injecting ASC after a random pattern skin flap will enhance viability as measured by decreased area of necrosis 91 . Further work demonstrated that this enhanced survival was based on neovascularization, with ASC distributing into new vascular networks and tubules 92,93 . These new vascular networks can be developed and arborized in a shorter period of time when aided by co‐culturing ASC with human adipose‐derived microvascular endothelial cells, as described by Freiman 61 .…”

“…91 Further work demonstrated that this enhanced survival was based on neovascularization, with ASC distributing into new vascular networks and tubules. 92,93 These new vascular networks can be developed and arborized in a shorter period of time when aided by co-culturing ASC with human adipose-derived microvascular endothelial cells, as described by Freiman. 61 This was further supported by Yu's group, who showed that ASC increased flap survival via regulation of the VEGF/HIF-1α pathway inducing neovascularlization.…”

Pharmacological and cell-based treatments to increase local skin flap viability in animal models

“…They can potentially provide a longer therapeutic effect window due to the self-renewing and differentiating capability of the cells. Additionally, mesenchymal stem cells (MSCs) can differentiate into endothelial cells to form new vessels and significantly lower necrosis rates in rat dorsal skin flaps in ischemia–reperfusion conditions, as shown by Foroglou et al [ 76 ].…”