Background Fat grafting, as a standard treatment for numerous soft tissue defects, remains unpredictable and technique-dependent. Human adipose-derived stem cells (hADSCs) are promising candidates for cell-assisted therapy to improve graft survival. As free-living fat requires nutritional and respiratory sources to thrive, insufficient and unstable vascularization still impedes hADSC-assisted therapy. Recently, cytotherapy combined with modified mRNA (modRNA) encoding vascular endothelial growth factor (VEGF) has been applied for the treatment of ischemia-related diseases. Herein, we hypothesized that VEGF modRNA (modVEGF)-engineered hADSCs could robustly enhance fat survival in a fat graft transplantation model. Methods hADSCs were acquired from lipoaspiration and transfected with modRNAs. Transfection efficiency and expression kinetics of modRNAs in hADSCs were first evaluated in vitro. Next, we applied an in vivo Matrigel plug assay to assess the viability and angiogenic potential of modVEGF-engineered hADSCs at 1 week post-implantation. Finally, modVEGF-engineered hADSCs were co-transplanted with human fat in a murine model to analyze the survival rate, re-vascularization, proliferation, fibrosis, apoptosis, and necrosis of fat grafts over long-term follow-up. Results Transfections of modVEGF in hADSCs were highly tolerable as the modVEGF-engineered hADSCs facilitated burst-like protein production of VEGF in both our in vitro and in vivo models. modVEGF-engineered hADSCs induced increased levels of cellular proliferation and proangiogenesis when compared to untreated hADSCs in both ex vivo and in vivo assays. In a fat graft transplantation model, we provided evidence that modVEGF-engineered hADSCs promote the optimal potency to preserve adipocytes, especially in the long-term post-transplantation phase. Detailed histological analysis of fat grafts harvested at 15, 30, and 90 days following in vivo grafting suggested the release of VEGF protein from modVEGF-engineered hADSCs significantly improved neo-angiogenesis, vascular maturity, and cell proliferation. The modVEGF-engineered hADSCs also significantly mitigated the presence of fibrosis, apoptosis, and necrosis of grafts when compared to the control groups. Moreover, modVEGF-engineered hADSCs promoted graft survival and cell differentiation abilities, which also induced an increase in vessel formation and the number of surviving adipocytes after transplantation. Conclusion This current study demonstrates the employment of modVEGF-engineered hADSCs as an advanced alternative to the clinical treatment involving soft-tissue reconstruction and rejuvenation.

Abstract Background Double eyelid blepharoplasty is the most popular cosmetic surgery among Asian population. Although various surgical procedures have been reported, limitations, including asymmetry or the disappearance of the double eyelid crease, an unnatural double eyelid crease curve and distinct scars, still exist in patients. Objectives The authors aim to provide a new technique to reduce the various complications of blepharoplasty mentioned above and to create dynamic, natural-looking double eyelids. Methods From September 2018 to June 2019, the new technique was performed on 92 Chinese patients. The core of our technique was to rebuild a reliable motion transmitter: the orbital septum-levator aponeurosis flap, which was sutured to the tarsus. The outcomes were assessed six months after the surgery by reviewing the medical records and the photographs to assess the aesthetic outcomes, the relapse rate and the incidence of complications. Results In the aesthetic outcome assessment, 86 patients were graded as good, four graded as fair, two patients among whom having uneven scars and the other two showing a slight asymmetry of the double eyelid curve in length or width. Two patients were graded as poor because of the disappearance of the double eyelid crease. The relapse rate was 2.2%. Two patients had temporary hematoma. Six patients had lagophthalmos that subsided within 30 days. No cases of infection or ptosis were observed. Conclusion The bridge technique is an effective method for creating dynamic, natural-looking double eyelids. However, the long-term outcome of this new surgical approach requires further study.

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Aim The study sought to determine whether extended forehead flap by using part of the scalp combined with laser hair removal is a practical approach when repairing distal nasal defect. Methods A retrospective study was conducted with 6 patients who underwent reconstruction of nasal defects with extended forehead flaps (including scalp combined with subsequent laser hair removal) at Shanghai Ninth People's Hospital between June 2016 and December 2018. Surgical data collected included age, causes of defects, sizes of defects, invaded nasal subunits, implantation of tissue expander, time elapsed between the formation of defects and surgical treatments, sessions of laser hair removal, and follow-up results. All patients had nasal defects after removal of a benign nevus (diameter, >1.5 cm), which invaded distal nasal subunits (including the nasal tip, soft triangle, columella, and nasal ala) and could not be repaired using adjacent tissue. Preoperative and postoperative assessments of esthetic outcomes were analyzed, including skin color and texture match, appearance deformity, and scar appearance. Results All 6 female patients (ages 4 to 24 years) accepted the extended forehead flap technique and subsequent laser hair removal treatments. Among the 6 patients, 2 had nasal tip defects, 1 had a columella nasi defect, one had an alar defect, and 2 had multiunit defects. All transferred forehead flaps survived with no necrosis and underwent 2 to 5 subsequent laser hair removal treatments. The color and texture of the transferred flaps was similar to the adjacent skin in all patients. All patients were satisfied with the final outcome of the reconstructed nose with no obvious scarring during follow-up. Conclusions Extending the forehead flap using the scalp is a practical and safe approach for the repair of large and distal nasal defects. Subsequent laser hair removal can eliminate the hair follicles of the scalp and improve the appearance and color of the flap.

Background Autologous adipose tissue transfer may be performed for aesthetic needs following the resection of dermatofibrosarcoma protuberans (DFSP), the most common cutaneous soft tissue sarcoma, excluding Kaposi sarcoma. The regenerative effectiveness of cell-assisted lipotransfer is dependent on the presence of adipose tissue-derived stem cells (ADSCs). This is the first study to evaluate the potential oncological risks as ADSCs could unintentionally be sited within the proximity of the tumor microenvironment of DFSP cells. Methods Primary DFSP cells were indirectly co-cultured with ADSCs in a conditioned medium or in a Transwell system. The impact was analyzed by assessing proliferation, migration, invasion, angiogenesis, and tumor-associated genes and proteins. Results of these assays were compared between co-culture and mono-culture conditions. Results Our experimental results showed that ADSCs were able to promote proliferation, migration, invasion, and angiogenesis of DFSP cells; this was accompanied by a significant increase in the expression levels of beta-type platelet-derived growth factor receptor, collagen type I alpha 1 chain, vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor. Conclusions The current report clearly demonstrates that ADSCs can enhance different malignant properties of DFSP cells in vitro, which should not be neglected when considering the clinical use of human ADSCs and its related derivatives in skin regenerative therapies.

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