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.</p

Transport of Live Cells under Sterile Conditions Using a Chemotactic Droplet

© 2018 The Author(s). 1-Decanol droplets, formed in an aqueous medium containing decanoate at high pH, become chemotactic when a chemical gradient is placed in the external aqueous environment. We investigated if such droplets can be used as transporters for living cells. We developed a partially hydrophobic alginate capsule as a protective unit that can be precisely placed in a droplet and transported along chemical gradients. Once the droplets with cargo reached a defined final destination, the association of the alginate capsule and decanol droplet was disrupted and cargo deposited. Both Escherichia coli and Bacillus subtilis cells survived and proliferated after transport even though transport occurred under harsh and sterile conditions

From low-conflict polity to democratic civil peace: Explaining Zambian exceptionalism

An absence of civil war and other significant sub-state violence makes Zambia an exceptional although not unique case in central-southern Africa. The literature devoted to explaining civil war has grown dramatically in recent years, but while it pays much attention to sub-Saharan Africa only rarely does it investigate counterfactual cases like Zambia. Similarly the growing field of research into post-conflict reconstruction fails to capture the distinct features of persistently low-conflict situations where many of the predisposing conditions for violent conflict might seem to be present. This paper examines Zambia’s experience against a background of general theories that try to explain conflict. It is an “interpretative case study”. The paper proceeds by substantiating Zambia’s claim to a relatively peaceful record and introduces ideas of conflict and conflict theories, before arguing that no single general theory dwelling on just one primary “cause” will suffice to explain Zambian exceptionalism. The precise mix of arguments differs for each one Zambia’s three republican eras, as the potential threats to peace have themselves evolved over the period since independence. The paper’s main theoretical claim is that over time the explanation is both multi-layered and dynamic. That said, certain features do stand out, most notably an inherited political culture that is predisposed against the violent resolution of conflict and continues to insulate the country against social and economic traumas and democratic shortcomings