Microencapsulated islet allografts in diabetic NOD mice and nonhuman primates.

OBJECTIVE: Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs). MATERIALS AND METHODS: Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy. Different transplant sites (intraperitoneal [i.p.], omental pouch, omental surface, and bursa omentalis) were tested in separate NHPs. Graft function was monitored by exogenous insulin requirements, fasting blood glucose levels, glucose tolerance tests, percent hemoglobin A1c (% HbA1c), and C-peptide levels. In vitro assessment of grafts included histology, immunohistochemistry, and viability staining; host immune responses were characterized by flow cytometry and cytokine/chemokine multiplex ELISAS. RESULTS: Microencapsulated islet allografts functioned long-term i.p. in diabetic NOD mice without immunosuppression, but for a relatively short time in immunosuppressed NHPs. In the NHPs, encapsulated allo-islets initially reduced hyperglycemia, decreased exogenous insulin requirements, elevated C-peptide levels, and lowered % HbA1c in plasma, but graft function diminished with time, regardless of transplant site. At necropsy, microcapsules were intact and non-fibrotic, but many islets exhibited volume loss, central necrosis and endogenous markers of hypoxia. Animals receiving supplemental oxygen and autologous MSCs showed improved graft function for a longer post-transplant period. In diabetic NHPs and mice, cell-free microcapsules did not elicit a fibrotic response. CONCLUSIONS: The evidence suggested that hypoxia was a major factor for damage to encapsulated islets in vivo. To achieve long-term function, new approaches must be developed to increase the oxygen supply to microencapsulated islets and/or identify donor insulin-secreting cells which can tolerate hypoxia.

Biological and performance variables in relation to age in male and female adolescent athletes.

To observe the cross-sectional nature of the effect of age, height, and body mass on motor performance during adolescence (13-18 years), 103 boy and 65 girl athletes were measured for motor performance and anthropometric variables. Motor performances included tests of strength, muscular endurance, flexibility, aerobic capacity, anaerobic power, speed, and agility. Anthropometric determinations included height, body mass, lean body mass, %fat, and somatotype. Boys were significantly different from girls in all measurements except endomorphy, while girls were significantly superior to boys only in flexibility. Physical maturation, as reflected by height and body mass, was a major contributor to increases in motor performance. Somatotype did not differ greatly across the age groups. Boys were significantly more mesomorphic than girls, while girls were significantly more ectomorphic than boys. Higher %fat and more endomorphy were significantly related to poorer performance for relative aerobic capacity, 40-yd dash, and agility in boys but only for upper body muscular endurance in girls. Mesomorphy had higher relationships with performance variables among boys than among girls. Growth would appear to contribute significantly to enhanced motor performance with age, and its effect may be different in boys than in girls.