Xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells improves diabetic wound healing by promoting angiogenesis and lymphangiogenesis.

BACKGROUND: Some clinical trials have shown the usefulness of stem cell therapy for diabetic foot ulcers. However, the donor supply is limited, and the process is time consuming and expensive. This study assessed the therapeutic effects of neonatal porcine bone marrow-derived mesenchymal stem cell (npBM-MSC) xenotransplantation using diabetic wound model mice. METHODS: All layers of back skin were removed from streptozotocin-induced diabetic mice. In the npBM-MSCs group, npBM-MSCs were transplanted to the wound, and syngeneic mouse bone marrow-derived mesenchymal stem cells (mBM-MSCs) were transplanted to the wound in the mBM-MSCs group. The control group comprised diabetic mice that did not receive cellular therapy. The therapeutic effects of the transplantation were evaluated according to the rate of wound closure and the promotion of neovascularization in the wound. RESULTS: The wound closure rate was significantly improved in the npBM-MSCs group compared with the control group (p < .001 at postoperative day [POD] 4 and p < .01 at POD 7) and mBM-MSCs groups (p < .05 at POD 4). Prominent promotion of both angiogenesis and lymphangiogenesis was observed in the npBM-MSCs group. Furthermore, the expression of murine Prox1 and both porcine and murine Vegfs and Tgfb1 in the wounds was enhanced until POD 4 by npBM-MSCs transplantation. The amounts of vascular endothelial growth factor (VEGF) A, VEGFC, and transforming growth factor ß1 secreted from npBM-MSCs were higher than those from mBM-MSCs (p < .05). CONCLUSION: Xenotransplantation of npBM-MSCs improved diabetic wound healing by promoting both angiogenesis and lymphangiogenesis.

Distinguishing features of body mass index and psoriasis in men and women in Japan: A hospital-based case-control study.

Psoriasis is a chronic inflammatory disease and recent studies reported an association between obesity and psoriasis. To further investigate the association between body mass index (BMI) and psoriasis, a hospital-based retrospective case-control study was conducted in patients at the Department of Dermatology, Fukuoka University Hospital in 1998-2012. BMI values of psoriatic patients were compared with those of controls, who had skin diseases other than psoriasis. A total of 429 psoriatic patients (295 male, 134 female) and 16 028 controls were enrolled. The number of male patients with psoriasis sharply increased in their 30s, peaked in their 50s and remained relatively high through the 60s. The number of female patients showed a gradual increase to their 60s. Mean BMI was higher in psoriatic patients (23.96 ± 4.46) than in controls (22.22 ± 3.98, P < 0.0001). Age-stratified mean BMI in psoriatic patients was significantly higher at different ages in each sex. The odds ratio for psoriasis was significantly higher in obese patients. Stratified by age, there was a high odds ratio for psoriasis in men in their 40s, 70s and 80s, and in women in their 20s, 30s and 70s. The study suggests that, apart from those with a genetic predisposition, young women are less likely to develop psoriasis unless they have a high BMI, while men are more likely to acquire psoriasis if they have mild obesity in middle or older age. Our data may partially explain the higher male : female ratio (usually 2:1) in Japanese psoriatic patients.

Edaravone, a free radical scavenger, accelerates wound healing in diabetic mice.

UNLABELLED: Refractory wound healing is a major complication of diabetes, which restricts wound healing by interfering with the inflammatory response, decreasing granulation, causing peripheral neuropathy, and inhibiting angiogenesis. Oxidative stress has been proposed as an important pathogenic factor in diabetic wound complications. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a strong free radical scavenger that suppresses the effect of oxidative stress. MATERIAL AND METHODS: Streptozotocin-induced diabetes was established in adult C57BL/6 mice, and full-thickness skin was then removed from the dorsomedial back using an 8-mm biopsy punch. Edaravone or vehicle alone was applied to the wound on day 0 and day 4 after wound creation. The wound was monitored with a digital camera and analyzed on days 0, 4, and 7 after wound creation. RESULTS: This study investigated whether accelerated wound closure occurred in the edaravone group (n = 24) compared with the vehicle-alone group (n = 15). On day 7, wound closure between the 2 groups was statistically different (P = 0.0019). Angiogenesis and lymphangiogenesis were markedly promoted. The possibility of an inhibitory effect of edaravone characterized by suppression of oxidative stress was explored. Edaravone-induced upregulation of endothelial nitric oxide synthase (eNOS) mRNA expression, and eNOS protein was immunohistochemically detected. CONCLUSION: Edaravone upregulates eNOS expression and accelerates wound healing.

Possible association of hepatitis C virus infection with late-onset psoriasis: a hospital-based observational study.

Psoriasis is a chronic inflammatory disease mainly involving the skin and joints, mediated by pro-inflammatory cytokine tumor necrosis factor (TNF)-α. In hepatitis C, continuous inflammation mediated by TNF-α leads to liver cirrhosis and diabetes mellitus. Hence, psoriasis and hepatitis C have pathophysiological factors in common. An epidemiological association between the two conditions has been reported, but no detailed research has yet been performed. Frequency of hepatitis C virus (HCV) infection was assessed in 717 patients with psoriasis and 38 057 with all other dermatological diseases who visited Fukuoka University Hospital in 1998-2011. HCV⁺ and HCV⁻ psoriatic patients were further compared. Frequency of HCV infection was significantly higher in psoriasis (7.5%) than in controls (3.3%) in overall ages. When stratified by age at the first visit, the frequency was significantly higher in patients with psoriasis than in controls aged in their 60s (11.8% vs 6.6%, respectively, P = 0.0215) and 70s (19.5% vs 7.3%, P < 0.0001). HCV⁺ psoriatic patients were significantly older at onset than HCV⁻ ones (median, 54 vs 39 years), stronger male predominance (male/female ratio, 4.4:1), similar family history of psoriasis, higher association of diabetes mellitus and hypertension, and significantly lower body mass index (22.4 ± 2.73 vs 24.2 ± 4.61), in age-stratified (≥ 40 years) analysis. HCV⁺ psoriatic patients were less obese, but still had a higher frequency of diabetes mellitus and hypertension, possibly due to chronic inflammation in the liver and other organs. HCV infection may trigger psoriasis, especially late-onset psoriasis, possibly via overproduction of TNF-α, a common mediator of the two conditions.