Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

(1) Background: Diabetes impairs angiogenesis and wound healing. Paracrine secretion from adipose stem cells (ASCs) contains membrane-bound nano-vesicles called exosomes (ASC-Exo) but the functional role and therapeutic potential of diabetic ASC-Exo in wound healing are unknown. This study aims to investigate the in vivo mechanistic basis by which diabetic ASC-Exo enhance cutaneous wound healing in a diabetic mouse model. (2) Methods: Topically applied exosomes could efficiently target and preferentially accumulate in wound tissue, and the cellular origin, ASC or dermal fibroblast (DFb), has no influence on the biodistribution pattern of exosomes. In vivo, full-thickness wounds in diabetic mice were treated either with ASC-Exo, DFb-Exo, or phosphate-buffered saline (PBS) topically. ASC-Exo stimulated wound healing by dermal cell proliferation, keratinocyte proliferation, and angiogenesis compared with DFb-Exo and PBS-treated wounds. (3) Results: Diabetic ASC-Exo stimulated resident monocytes/macrophages to secrete more TGF-β1 and activate the TGF-β/Smad3 signaling pathway. Fibroblasts activated by TGF-β1containing exosomes from ASCs initiate the production of TGF-β1 protein in an autocrine fashion, which leads to more proliferation and activation of fibroblasts. TGF-β1 is centrally involved in diabetic ASC-Exo mediated cellular crosstalk as an important early response to initiating wound regeneration. (4) Conclusions: The application of diabetic ASC-Exo informs the potential utility of a cell-free therapy in diabetic wound healing.

To evaluate the functional and oncological outcomes of anterolateral thigh flap reconstruction for salvage laryngopharyngectomy after concurrent chemoradiotherapy for patients with hypopharyngeal carcinoma. A retrospective review was conducted on patients who underwent pharyngoesophageal reconstruction using anterolateral thigh flap after salvage laryngopharyngectomy for recurrent hypopharyngeal carcinoma between June 2003 and May 2010 at Chang Gung Memorial Hospital. The perioperative morbidity, mortality, functional outcomes, and oncological outcomes were evaluated. 33 patients were entered into the study. The mean follow-up time was 19.5±12.3 months. Recurrent pathological TNM stages included 3 (9.1%), 2 (6.1%), and 28 (84.8%) patients with stage II, III, and IV disease, respectively. Mean ICU stay was 10.3 days and the mean hospital stay was 39.9 days. Peri-operative mortality occurred in one patient (3%). 16 patients (48.5%) developed recipient site complications. Among them, 14 patients (42.4%) developed fistulas and 9 patients (27.3%) developed strictures. Except for 4 patients (12.1%), all achieved varying degree of oral intake with 29 patients (60.6%) being completely independent from tube feeding. The mean interval to start oral intake was 15.1 days. The 5-year overall survival and disease–free survival rates were 51.8% and 53.7%, respectively. The pN status is an independent predictor of overall survival and disease–free survival (P = 0.027 and 0.038, respectively). Pharyngoesophageal reconstruction after salvage laryngopharyngectomy remains challenging even in the experienced hands. Reconstructive microsurgeons who are prepared to take on these cases should be equally well prepared to manage the potential postoperative complications.

Background: Depression is common among patients with head and neck cancer, thereby affecting their survival rate. However, whether close monitoring of depression affects the survival outcomes of these patients is unknown. Therefore, this study aimed to determine whether depression treatment continuity after the diagnosis of cancer affects the survival of these patients.Methods: A total of 55,069 patients diagnosed with head and neck cancer in the Cancer Registration System database in Taiwan were enrolled. This cohort was followed from January 1, 2007 to December 31, 2017. Furthermore, the patients were divided into four groups, namely, “no depression,” “pre-cancer only,” “post-cancer only,” and “both before and after cancer,” on the basis of the diagnosis of depression and the duration of the follow-up period in the psychiatric clinic. Further, the Cox proportional hazard model was applied to estimate the hazard of death for the four groups.Results: A total of 6,345 (11.52%) patients were diagnosed with depression in this cohort. The “pre-cancer only” group had a lower overall survival (HR = 1.18; 95% CI = 1.11–1.25) compared with the “no depression” group. Moreover, the “post-cancer only” group had better overall survival (HR = 0.88; 95% CI = 0.83–0.94) compared with the “no depression” group, especially in advanced-stage patients. Patients who were diagnosed with depression before cancer and had continuous depression treatments after the cancer diagnosis had better overall survival (HR = 0.78; 95% CI = 0.71–0.86) compared with patients who had treatment interruptions.Conclusion: Patients with pre-cancer depression had poorer survival outcomes, especially those who did not receive psychiatric clinic visits after their cancer diagnosis. Nonetheless, in patients with advanced-stage cancer, depression treatment may improve overall survival.