Cell-based therapy is an attractive approach for the treatment of chronic nonhealing wounds. This study investigated whether adipose-derived stem cells (ASCs) can accelerate diabetic wound healing and traffic in the engraftment of ASCs. Dorsal full-thickness skin wound defects (6 × 5 cm) were created in a streptozotocin (STZ)-induced diabetes rodent model. Group I served as a nondiabetic normal control, group II served as a diabetic control without ASCs, and group III included rats that were injected subcutaneously in the wound margin twice with nondiabetic ASCs (1 × 107 ASCs/dose). The wound healing was assessed clinically. Histological examination and immunohistochemical analyses of periwound tissue were performed. Green fluorescence protein (GFP)+-ASCs were used to examine the engraftment of these cells after injection. XenoLight DiR-labeled ASCs were implanted to detect migration ability using an IVIS imaging system. Results revealed that complete wound healing time statistically decreased in the ASC-treated group compared to the controls (p < 0.001). Histological examination revealed the ASC-treated group showed a significant reduction in the proinflammatory reaction, with significantly increased levels of EGF, VEGF, rPH, and Ki-67 expression compared to the controls. The populations of GFP+-ASCs in circulating blood significantly increased after ASC injection compared to those of controls. Immunofluorescence staining showed GFP+-ASCs significantly accumulated in the subdermal layer of the wound margin and increased angiogenesis via vWF and VEGF expression after injection. IVIS analysis revealed ASCs could exist and home into the periwound area up to 8 weeks postimplantation. In conclusion, ASCs significantly enhanced diabetic wound healing, engrafted into the local wound tissue, and implanted into circulating blood. ASC treatment stimulated neoangiogenesis and increased tissue regeneration through paracrine and autocrine mechanisms.
1 January 2004 in Plastic and Reconstructive Surgery
Large, full-thickness lip defects after head and neck surgery continue to be a challenge for reconstructive surgeons. The reconstructive aims are to restore the oral lining, the external cheek, oral competence, and function (i.e., articulation, speech, and mastication). The authors' refinement of the composite radial forearm-palmaris longus free flap technique meets these criteria and allows a functional reconstruction of extensive lip and cheek defects in one stage. A composite radial forearm flap including the palmaris longus tendon was designed. The skin flap for the reconstruction of the intraoral lining and the skin defect was folded over the palmaris longus tendon. Both ends of the vascularized tendon were laid through the bilateral modiolus and anchored with adequate tension to the intact orbicularis muscle of the upper lip. This procedure was used in 12 patients. Six patients had cancer of the lower lip, five patients had a buccal cancer involving the lip, and one patient had a primary gum cancer that extended to the lower lip. Total to near-total resection (more than 80 percent) of the lower lip was indicated in six patients. In two other patients, the cancer ablation included more than 80 percent of the lower lip and up to 40 percent of the upper lip. A radial forearm palmaris longus free flap was used in all cases for reconstruction of the defect. Free flap survival was 100 percent. At the time of final evaluation, which was 1 year after the operation, all patients had good oral continence at rest (static suspension) and had achieved sufficient oral competence when eating. Ten patients were able to resume a regular diet, and two patients could eat a soft diet. All patients regained normal or near-normal speech and had an acceptable appearance. The described refinement of the composite radial palmaris longus free flap technique allows the reconstruction of the lower lip with a functioning oral sphincter; the technique can be recommended for patients who need large lower lip resection. It provides functional recovery of the reconstructed lower lip synchronizing with the remaining upper lip.
1 October 2011 in Plastic and Reconstructive Surgery
This study investigated whether bone marrow–derived mesenchymal stem cell therapy has effectiveness in the enhancement of diabetic wound healing through tissue regeneration. The authors used a dorsal skin defect (6 × 5 cm) in a streptozotocin-induced diabetes rodent model. Forty male Wistar rats were divided into four groups: group I, nondiabetic rats (controls); group II, diabetic controls receiving no mesenchymal stem cells; group III, rats receiving 1 × 107 stem cells per dose (subcutaneously administered in eight areas surrounding wound margin) on day 7; and group IV, rats receiving stem cells on days 7 and 10. Wound healing was assessed clinically. Histologic examination was performed with hematoxylin and eosin staining. CD45, Ki-67, prolyl 4-hydroxylase, epidermal growth factor, and vascular endothelial growth factor were evaluated with immunohistochemical analysis. Overall clinical results showed that wound size was significantly reduced in mesenchymal stem cell–treated rats as compared with controls. Complete wound-healing time was statistically shorter in rats treated once as compared with controls (6.6 ± 1.13 weeks versus 9.8 ± 0.75 weeks; p < 0.001). It was significantly shorter in rats treated with mesenchymal stem cells twice as compared with rats treated once (5.2 ± 0.75 weeks versus 6.6 ± 1.13 weeks; p = 0.026). Histologic analysis revealed significant reduction in topical proinflammatory reaction and suppression of CD45 expression in the mesenchymal stem cell group as compared with the control group. On immunohistochemistry analysis, significant increases in epidermal growth factor, vascular endothelial growth factor, prolyl 4-hydroxylase, and Ki-67 expression were noted in the treated group as compared with the control group. Mesenchymal stem cells significantly enhanced diabetic wound healing. Treatment with them is associated with increases of biomarkers in tissue regeneration.