Enhanced insulin production and reprogramming efficiency of mesenchymal stem cells derived from porcine pancreas using suitable induction medium.

BACKGROUND: Genetic reprogramming is a powerful method for altering cell properties and inducing differentiation. However, even if the same gene is reprogrammed, the results vary among cells. Therefore, a better possible strategy involves treating cells with factors that further stimulate differentiation while using stem cells with the same tissue origin. This study aimed to increase induction efficiency and insulin production in reprogrammed cells using a combination of factors that promote cell differentiation. METHODS: Porcine pancreatic cells were cultured to obtain mesenchymal stem cells expressing pancreatic cell-specific markers through sequential passages. The characteristics of these cells were identified, and the M3 gene (Pdx1, Ngn3, MafA) was reprogrammed to induce differentiation into insulin-producing cells. Additionally, the differentiation efficiency of insulin-producing cells was compared by treating reprogrammed cells with a differentiation-promoting factor. RESULTS: Mesenchymal stem cells isolated from porcine pancreatic tissues expressed exocrine cell markers, including amylase and cytokeratin 18, and most cells continuously expressed the beta cell transcription factors Ngn3 and NeuroD. Reprogramming of the M3 gene resulted in differentiation into insulin-producing cells. Moreover, significantly increased insulin and glucagon expressions were observed in the suitable induction medium, and the characteristic beta cell transcription factors Pdx1, Ngn3, and MafA were expressed at levels as high as those in pancreatic islet cells. CONCLUSIONS: Differentiation into insulin-producing cells represents an alternative therapy for insufficient pancreatic islet cells when treating diabetes. Therefore, cells with the characteristics of the target cell should be used to improve differentiation efficiency by creating an environment that promotes reprogramming and differentiation.

Treatment of chemically induced oral ulcer using adipose-derived mesenchymal stem cell sheet.

BACKGROUND: This study investigated the effects of mesenchymal stem cell (MSC) sheet transplantation on healing of chemically induced oral ulceration in a rabbit animal model. METHODS: Oral mucosal ulcers were induced by topical application of filter paper soaked with 70% acetic acid to the anterior gingiva and buccal mucosa of 12 New Zealand white rabbits. The animals were randomly assigned to two groups: with (treatment group, n = 6) or without (control group, n = 6) cell sheets applied to ulcers. Gross findings were sequentially evaluated, and histologic examination was performed on day 7. RESULTS: Based on gross inspection, ulceration resolved before day 5 in the treatment group; however, in the control group, healing was incomplete on day 7. In the treatment group, the total area of the ulcer decreased significantly from day 2 to day 5 (P < 0.001) and from day 5 to day 7 (P = 0.020), whereas the area decreased significantly from day 5 to day 7 in the control group (P < 0.001). Histologic and immunofluorescence examination revealed full-thickness mucosa healing and complete basal cell coverage in the treatment group; in contrast, only partial healing was observed on day 7 in the control group. CONCLUSIONS: Cell sheet technology using MSC can be an alternative treatment for oral ulcerations in that it can decrease healing time without invasive properties.

A Combination Treatment of Raloxifene and Vitamin D Enhances Bone-to-Tendon Healing of the Rotator Cuff in a Rat Model.

BACKGROUND: Tearing and degeneration of the rotator cuff at the tendon-to-bone junction are common in adults aged ≥50 years. Few studies have reported on the relationship between estrogen and the rotator cuff enthesis. In addition to preventing bone loss, selective estrogen receptor modulators have been shown to improve tendon and muscle quality. PURPOSE: To evaluate the effects of raloxifene (RLX) and vitamin D on rotator cuff tendon-to-bone healing in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 29 female rats (58 shoulders) were assigned to 4 groups: (1) control group, (2) ovariectomy (OVX)-only group, (3) no RLX group (OVX and rotator cuff repair [RCR]), and (4) RLX group (OVX, RCR, and RLX). Rats that did not undergo rotator cuff tear (RCT) surgery were divided into the control and OVX-only groups according to OVX surgery. Rats that underwent RCT surgery and RCR were divided into the no RLX and RLX groups according to RLX and vitamin D administration. An estrogen-deficient state was induced by OVX at 12 weeks of age. Bone mineral density (BMD) and trabecular bone characteristics were measured by micro-computed tomography, and healing of the tendon-to-bone junction was evaluated by biomechanical testing, histomorphometry, and micro-magnetic resonance imaging (MRI). RESULTS: The mean final body weight (BW; 461.6 ± 47.3 g) of the OVX-only group was significantly higher and BMD (0.25 ± 0.07 g/cm3) was significantly lower (P < .001) than the mean final BW (338.5 ± 35.1 g) and BMD (0.48 ± 0.05 g/cm3) of the control group. In contrast, the RLX group showed that the BW (369.6 ± 35.8 g) and BMD (0.41 ± 0.08 g/cm3) were not significantly different from the control group. The RLX group had a significantly higher histomorphometric total score (8.50 ± 1.05) than the no RLX group (4.83 ± 2.48). On biomechanical testing, the RLX group (29.7 ± 9.1 N) showed a significantly higher load to failure than the no RLX group (19.4 ± 8.8 N). On micro-MRI, the RLX group had a more homogeneous low signal and tendon continuity than the no RLX group. CONCLUSION: The combination treatment of RLX and vitamin D prevented a decrease in local BMD (greater tuberosity of the proximal humerus) and enhanced tendon-to-bone healing of the rotator cuff in a rat model. CLINICAL RELEVANCE: This study induced an estrogen-deficient state similar to the human postmenopausal state and used drugs that are actually being prescribed in a clinical situation.

Impact of Gender on the Association of Epicardial Fat Thickness, Obesity, and Circadian Blood Pressure Pattern in Hypertensive Patients.

This study aimed to investigate the effects of gender on the association between epicardial fat thickness (EFT) and circadian blood pressure (BP) changes in patients with recently diagnosed essential hypertension (EH). A total of 441 patients with EH (male/female: 236/205, mean age: 50.7 ± 13.8) and 83 control patients underwent 24-hour ambulatory BP monitoring and echocardiography. Obese EH patients had higher circadian BP profile with BP variability, wall thickness, and left ventricular mass than nonobese EH patients and controls (all p's <0.05) without gender differences. EFT was higher in female than in male patients (7.0 ± 2.5 versus 5.9 ± 2.2 mm, p < 0.001) and higher in the obese female EH group (7.5 ± 2.6 mm) than in the control (6.4 ± 2.8 mm) or nonobese EH group (6.7 ± 2.8 mm) among women, whereas EFT did not vary among males (5.9 ± 1.9 versus 6.0 ± 2.7 versus 5.9 ± 2.4 mm, p = 0.937). Multivariate logistic regression analysis demonstrated that the 24-hour mean BP variability was associated with SBP (p = 0.018) and EFT (p = 0.016) in female patients, but not in male patients. The relationships among circadian BP variability, obesity, and EFT were affected by gender in different manners. EFT may be a more valuable parameter in the evaluation of BP severity and obesity in women than in men.

A case of persistent apical ballooning complicated by apical thrombus in takotsubo cardiomyopathy of systemic lupus erythematosus patient.

Takotsubo cardiomyopathy, which is also known as "transient apical ballooning", is a cardiac syndrome associated with emotional and physical stress that occurs in postmenopausal women. It may mimic acute coronary syndrome but coronary angiography reveals normal epicardial coronary arteries. The prognosis is favorable with the normalization of wall motion abnormalities within weeks. We report a case of persistent apical ballooning complicated by an apical thrombus in Takotsubo cardiomyopathy of systemic lupus erythematous patient. Takotsubo cardiomyopathy may not be always transient and left ventricular thrombus can occur in the disease course as our patient.

[A case of superior mesenteric artery syndrome caused by anorexia nervosa].

Superior mesenteric artery (SMA) syndrome is a rare disorder, characterized by compression of the third segment of the duodenum by the mesenteric artery at the level of the SMA, resulting in duodenal dilatation. Precipitating factors of the SMA syndrome include prolonged bed rest, weight loss, abdominal surgery, and increased lordosis of the spine. We report a case of SMA syndrome caused by anorexia nervosa in a 15-year-old adolescent girl. CT and an upper gastrointestinal contrast series revealed partial obstruction of the third portion of duodenum and decreased aortomesenteric distance. The patient's symptoms were successfully treated with total parental nutrition and psychiatric treatment including supportive, cognitive behavioral therapy and antidepressant medication. This case shows that SMA syndrome is an unusual gastrointestinal complication that may occur in patients with anorexia nervosa.

Injectable polysaccharide microcapsules for prolonged release of minocycline for the treatment of periodontitis.

Injectable polysaccharide microcapsules holding minocycline were fabricated from alginate and chitosan for the treatment of periodontitis. The microcapsules were examined for the release and degradation of minocycline, as well as antimicrobial activity. The microcapsules were biodegradable and released minocycline between 10 and 1000 microg ml(-1), which was higher than the usual therapeutic concentration (1-5 microg ml(-1)), for up to 7 days. These microcapsules showed a statistically significant suppression of pathogenic bacteria, such as Prevotella intermedia causing periodontitis. The microcapsules are thus potentially useful for drug delivery for the treatment of periodontitis.