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Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing β-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation.

Islet transplantation is a treatment modality for diabetes mellitus that can maintain insulin levels within a physiologically appropriate range. However, wider clinical application is limited by insufficient donor numbers and a need for lifelong immunosuppression. Despite various clinical and preclinical trials, there is no single standard immunosuppressive regimen that can suppress acute and chronic immune reactions with lower toxicity to grafted islets. One of the strategies for overcoming lifelong immunosuppression is the incorporation of encapsulation technology, which can provide a physical immune barrier by keeping out high molecular weight immune system components, while still allowing low molecular weight oxygen, insulin and nutrients to pass through. Encapsulated islet transplantation approaches that have been studied so far include macroencapsulation, microencapsulation, conformal coating and nanoencapsulation. Herein we will review the basic concepts of islet encapsulation technique, earlier works to recent progress related to clinical studies and corporate investigations on encapsulated islet transplantation.

Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end‐organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life‐long need for often‐toxic antirejection drugs. Coadministering islets with bone marrow‐derived mesenchymal stem cells (MSCs) that exert robust immune‐modulating, anti‐inflammatory, anti‐apoptotic, and angiogenic actions, improves intrahepatic islet survival and function. Encapsulation of insulin‐producing cells to prevent immune destruction has shown both promise and failures. Recently, stem cell‐derived insulin secreting β‐like cells induced euglycemia in diabetic animals, although their clinical use would still require encapsulation or anti‐rejection drugs. Instead of focusing on further improvements in islet transplantation, we demonstrate here that the intraperitoneal administration of islet‐sized “Neo‐Islets” (NIs), generated by in vitro coaggregation of allogeneic, culture‐expanded islet cells with high numbers of immuno‐protective and cyto‐protective MSCs, resulted in their omental engraftment in immune‐competent, spontaneously diabetic nonobese diabetic (NOD) mice. This achieved long‐term glycemic control without immunosuppression and without hypoglycemia. In preparation for an Food and Drug Administration‐approved clinical trial in dogs with T1DM, we show that treatment of streptozotocin‐diabetic NOD/severe combined immunodeficiency mice with identically formed canine NIs produced durable euglycemia, exclusively mediated by dog‐specific insulin. We conclude that this novel technology has significant translational relevance for canine and potentially clinical T1DM as it effectively addresses both the organ donor scarcity (>80 therapeutic NI doses/donor pancreas can be generated) and completely eliminates the need for immunosuppression. Stem Cells Translational Medicine 2017;6:1631–1643 Cultured, passaged islet cells and immune modulating MSCs are cocultured (A) to form allogeneic “Neo‐Islets” (B) that when delivered i.p. to recipients with autoimmune Type 1 diabetes mellitus, engraft in the omentum, redifferentiate to physiologically secrete insulin into the portal system, and normalize blood glucose long term without the need for immunosuppressive agents.

Purpose of Study Although the current treatment option of exogenous insulin administration for type 1 diabetes mellitus (T1DM) corrects hyperglycemia, it has its own limitations and complications in long-term use. Thus, alternative approaches such as immune therapies, glucose transporter inhibitors, gastro-enteric protein-hormone pathway modulators, and cell- and tissue-based therapies are being developed. Among these therapies, islet transplantation has been shown to be a more physiological means of treating type 1 diabetes. However, the shortage of donor tissues and the use of immunosuppressive agents have led to the development of immune isolation techniques such as cell encapsulation. Recent findings Although macroencapsulation of islets has been shown with some success, microencapsulation mostly with permselectively coated alginate hydrogel has been demonstrated to be superior among the variety of developed encapsulation technologies including nanoencapsulation and thus, has led to several clinical trials. While microencapsulated islet transplantation has shown promise in correcting the pathological symptoms of T1DM, the technology still requires improvement in a few areas in order to achieve sustained performance in long-term application. Summary Some approaches suggested for improvement include incorporation of immunomodulatory stem cells such as mesenchymal stem cells, substitution of current crosslinking agents with stable safe divalent cations, improving the chemistry of alginate by adding functional groups, and including extracellular matrix (ECM) components of the pancreas in the encapsulated islet construct. With thorough investigation and improvement on the pitfalls of the technology, and more clinical trials, the microencapsulation technology would provide a viable option for a sustainable and more physiological means of insulin delivery in T1DM.

Aim of the work was to study possibility of erythropoiesis stimulation by transplantation of fetal liver cells, seeded into macro¬porous carriers to the rats with post-hemorrhargic anemia, induced by 70% hepatectomy. Fetal liver cells (FLC) were isolated from fetuses of rats with 15 days’ gestation and were cryopreserved. Decryopreserved FLC were seeded into macroporous spongy alginate-gelatin scaffolds, which were covered by alginate capsule and implanted into omentum of rats with modeled liver insufficiency. It was shown that fetal liver cells, immobilized in macroporous scaffolds after implantation have positive effect on red blood count and hemoglobin content, indicating that this approach is promising for the development of new methods of anemia treatment.

Aim of the work was to study possibility of erythropoiesis stimulation by transplantation of fetal liver cells, seeded into macro­porous carriers to the rats with post-hemorrhargic anemia, induced by 70% hepatectomy. Fetal liver cells (FLC) were isolated from fetuses of rats with 15 days’ gestation and were cryopreserved. Decryopreserved FLC were seeded into macroporous spongy alginate-gelatin scaffolds, which were covered by alginate capsule and implanted into omentum of rats with modeled liver insufficiency. It was shown that fetal liver cells, immobilized in macroporous scaffolds after implantation have positive effect on red blood count and hemoglobin content, indicating that this approach is promising for the development of new methods of anemia treatment.

Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2 /neu-expressing tumors in mice by delivering an interleukin-2 fusion protein (sFvIL-2), or angiostatin. However, treatment with interleukin-2 led to profuse inflammation, while angiostatin delivery did not result in long-term tumor suppression, in part due to endothelial cell-independent neovascularization (vascular mimicry). We hypothesize that coencapsulating the two producer cells in the same microcapsules may enhance the efficacy and ameliorate the above side effects. Hence, B16-F0/neu tumor-bearing mice were implanted with sFvIL-2- and angiostatin-secreting cells coencapsulated in the same alginate-poly- L -lysine-alginate microcapsules. However, this protocol only produced an incremental but not synergistic improvement, as measured with greater tumor suppression and improved survival. Compared to the single sFvIL-2 treatment, the coencapsulation protocol showed improved efficacy associated with: mobilization of sFvIL-2 from the spleen; a higher level of cytokine delivery systemically and to the tumors; increased tumor and tumor-associated endothelial cell apoptosis; and a reduced host inflammatory response. However, compared to the single angiostatin treatment, the efficacy was reduced, primarily due to a “bystander” effect in which the angiostatin-secreting cells suffered similar transgene silencing as the coencapsulated cytokine-secreting cells. Nevertheless, the level of “vascular mimicry” of the single angiostatin treatment was significantly reduced. Hence, while there was no synergy in efficacy, an incremental improvement and some reduction in undesirable side effects of inflammation and vascular mimicry were achieved over the single treatments.

Although HIV prevalence in South Asia is relatively low, the epidemic is growing among marginalized groups, including sex workers, injection drug users, men who have sex with men, and transgender communities. Despite prevention and other efforts to reduce high-risk behaviors such as unprotected sex, buying and selling of sex, and injecting drug use, HIV vulnerability and risk remain high. This problem is partly due to a widespread failure to respond adequately to key social drivers of HIV: stigma and discrimination. Stigmatizing attitudes in the general population and discriminatory treatment by actors ranging from health providers to local policy makers intensify the marginalization of vulnerable groups at highest risk, driving them further from the reach of health services and much-needed prevention, treatment, care, and support. Daily harassment and abuse also cause health problems and adversely affect mental health, thereby leading to depression, social isolation, and an array of adverse socioeconomic outcomes related to HIV and AIDS. The South Asia Region Development Marketplace1 (SARDM) took an innovative and unique approach to addressing these gaps and needs through its 2008 development marketplace, \"tackling HIV and AIDS stigma and discrimination.\" Part one of this reports describes key findings and lessons learned that emerged across the 26 implementers. Part two contains case studies for six of the implementers, offering a more in-depth look at the lessons and challenges of intervening against stigma and discrimination. Part three provides summaries of all 26 projects.

The World Bank approaches malaria not only as a major public health issue but also as a broader development problem that costs Africa US12 billion a year and helps keep families and communities in poverty. In 2005, the World Bank reaffirmed its commitment to malaria control by launching the Booster Program for Malaria Control in Africa, a 10-year initiative that in its first three years committed over US470 million to malaria control on the continent. Focusing on a two-pronged approach of combining disease control interventions and health systems strengthening, the program has contributed significantly to the global effort to fight the disease.As Phase II (2008-2011) of the program begins, the World Bank will intensify its efforts to enable more countries in Africa to achieve and sustain large-scale impact on malaria. Major reductions in malaria deaths and illness are possible within the next five to seven years. Attacking the disease full-force with a front-loaded effort will have tremendous impact on health and economic outcomes. African nations and the global community are gearing up to meet this goal. As one of the top three funders of malaria control, the World Bank is called to play a lead role in this effort. Phase II of the Booster Program for Malaria Control in Africa is the Bank’s affirmative and emphatic response to this call.

Battling HIV/AIDS sets out principles and provides advice on the procurement of HIV/AIDS medicines and related supplies for programs scaling up antiretroviral therapy (ART) and associated health services. This technical guide examines the elements required to establish and ensure continuity of supplies, including medicines and other commodities. It provides extensive guidance on key topics: Quality Assurance, Selection & Quantification methods, Intellectual Property Rights, Procurement Strategies, Pricing & Financing, the Supply Cycle and Policy Issues. Specializing in procurement for HIV-related programs, Battling HIV/AIDS is a valuable resource for implementing agencies and donors dealing with HIV/AIDS related procurement, as it: focuses on resource-poor settings with little experience of treatment programs that include ART. discusses newer and more expensive drugs and tests required for ART, which because of cost or scale, have not yet become part of essential medicines policy in many countries. draws attention to some of the unpredictable factors associated with the scaling up of ART such as rapid growth in demand, the appearance of new medicines and tests, and sudden changes in markets. provides practical advice on intellectual property rights, a complex but important subject, laying out in simple terms the array of options available to national governments. provides references to valuable materials and offers links to readily available instructions and documentation.