Human embryonic stem cells (hESCs) are considered a potential alternative to cadaveric islets as a source of transplantable cells for treating patients with diabetes.

Efficient differentiation of hESC-derived pancreatic endocrine cells can occur in a macroencapsulation device, yielding glucose-responsive insulin-producing cells capable of reversing diabetes.

Patients with untreated obstructive sleep apnea hypopnea (OSAH) are predisposed to developing hypertension, and therapy with continuous positive airway pressure (CPAP) may reduce blood pressure (BP). The purpose of this study was to assess the impact of CPAP therapy on BP in patients with OSAH. We performed a comprehensive literature search up to July 2006 [Medline, PubMed, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane controlled trials register (CCTR), and Database of Abstract and Reviews of Effect (DARE)] to identify clinical studies and systemic reviews that examined the impact of CPAP on BP. Studies were included if they (1) were randomized controlled trials with an appropriate control group, (2) included systolic and diastolic BP measurements before and after CPAP/control in patients with OSAH, and (3) contained adequate data to perform a meta-analysis. To calculate pooled results, studies were weighted by inverse variances, with either a fixed or a random effects model used depending on the presence of heterogeneity (assessed with Q test). Ten studies met our inclusion criteria (587 patients): three studies were crossover (149 patients) and seven were parallel in design. Seven studies (421 patients) used 24-h ambulatory BP and three used one-time measurements. Two studies were of patients with heart failure (41 patients). Overall, the effects of CPAP were modest and not statistically significant; CPAP (compared to control) reduced systolic BP (SBP) by 1.38 mmHg (95% CI: 3.6 to -0.88, p = 0.23) and diastolic BP (DBP) by 1.52 mmHg (CI: 3.1 to -0.07; p = 0.06). Six of the trials studied more severe OSAH (mean AHI > 30/h, 313 patients); in these six trials, CPAP reduced SBP by 3.03 mmHg (CI 6.7 to -0.61; p = 0.10) and DBP by 2.03 mmHg (CI: 4.1 to -0.002; p = 0.05). There was a trend for SBP reduction to be associated with CPAP compliance. In unselected patients with sleep apnea, CPAP has very modest effects on BP. However, we cannot exclude the possibility that certain subgroups of patients may have more robust responses-this may include patients with more severe OSAH or difficult-to-control hypertension. Future randomized controlled trials in this area should potentially concentrate on these subgroups of patients.

Type 1 diabetes is a progressive autoimmune disease that is largely silent in its initial stages. Yet, sensitive methods for detection of β-cell death and prediction and prevention of diabetes are lacking. Micro-RNAs (miRNAs) have been found at high concentrations in body fluids. Here in this study we sought to determine whether an islet enriched miRNA, miR-375, is a suitable blood marker to detect β-cell death and predict diabetes in mice. We measured miR-375 levels by quantitative RT-PCR in plasma samples of streptozotocin (STZ)-treated C57BL/6 mice and nonobese diabetic (NOD) mice. We also measured miR-375 levels in media samples of cytokine- or STZ-treated islets in the presence or absence of cell-death inhibitors. High-dose STZ administration dramatically increased circulating miR-375 levels, prior to the onset of hyperglycemia. Similarly, in the NOD mouse model of autoimmune diabetes, circulating miR-375 levels were significantly increased 2 weeks before diabetes onset. Moreover, cytokine- and STZ-induced cell death in isolated mouse islets produced a striking increase in extracellular miR-375 levels, which was reduced by cell death inhibitors. These data suggest that circulating miR-375 can be used as a marker of β-cell death and potential predictor of diabetes.

In this pilot study there were potential improvements in a variety of cardiovascular biomarkers with CPAP. CPAP compliance was reasonably good even though patients were not particularly sleepy. Accordingly, larger randomized controlled trials in this area appear feasible and warranted.

SummaryPluripotent human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose-responsive human C-peptide secretion by 19–21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature β cell markers compared with mice. Moreover, ECM-related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation.

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We conclude that imatinib treatment reduces radiation-induced mast cell influx into the lungs and delays the alveolitis or fibrosis response of mice.