We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulation blockade regimen achieved sustained insulin independence (median survival, >140 days) without evidence of porcine endogenous retrovirus dissemination. Thus, neonatal porcine islets represent a promising solution to the crucial supply problem in clinical islet transplantation.

Nearly 600 cases of laparoscopic adrenalectomy have been described in the world literature, documenting the safety and effectiveness of the procedure. Comparative studies have demonstrated the advantages of the laparoscopic approach when compared to traditional open approaches to adrenalectomy, documenting a more rapid and comfortable recovery, shorter hospitalization, and fewer complications. Several techniques of laparoscopic adrenalectomy have been described. We prefer the transabdominal approach in the lateral decubitus position. Herein we report our experience with 28 adrenalectomies using this approach. Indications for adrenalectomy have been hyperaldosteronism (9), hypercortisolism (4), pheochromocytoma (3), incidentaloma (6), metastasis (3), lymphoma (1), angiomyolipoma (1), other (1). Average tumor size was 3.3 cm (1. 4-8.3 cm). Average operative time was 152 minutes (110-210 minutes), with left adrenalectomy taking slightly longer to perform than on the right (156 vs. 145 minutes). There were no intraoperative complications and one conversion to open adrenalectomy for a large metastatic lung cancer found to be invading the liver. One patient experienced left rib pain from a cannula site immediately at the costal margin. There were no other complications. Average length of hospitalization was 2.3 days (1-6 days). With this and others' experience, laparoscopic adrenalectomy has become the gold standard for adrenalectomy. This manuscript reviews the literature on laparoscopic adrenalectomy and describes the transabdominal lateral approach.

Objective-The purpose of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) levels and the prevalence of peripheral arterial disease (PAD) 4 Basic science research indicates that low vitamin D levels may be linked with cardiovascular risk. Vascular smooth muscle cells possess the 1-␣ hydroxylase enzyme that locally activates circulating vitamin D. 5 In animal models, active vitamin D is an inhibitor of the renin-angiotensin system 6 and myocardial cell hypertrophy. 7 Cellular experiments show that active vitamin D and its analogs exhibit anticoagulant activity. 8 Conflicting data are available on the association between low 25(OH)D levels and cardiovascular disease in the general population. 9 -11 Among adults, 25-hydroxyvitamin D (25(OH)D) levels Ն30 ng/mL are considered optimal. 12 These levels are associated with reduced fracture rates and have been postulated to be associated with better health outcomes. 12 The goal of the current study was to evaluate the association between serum 25(OH)D levels and the prevalence of PAD in the general population. To accomplish this goal, we analyzed data from a nationally representative sample of the United States adult population aged Ն40 years in NHANES 2001 to 2004. In addition, elevated serum calcium, phosphate, and intact parathyroid hormone (iPTH) levels have been associated with cardiovascular disease in the general population. 13,14 Because these serum markers are associated with vitamin D levels, we assessed the association between these serum markers and PAD in a secondary analysis.

BackgroundStem cells for cardiac repair have shown promise in preclinical trials, but lower than expected retention, viability, and efficacy. Encapsulation is one potential strategy to increase viable cell retention while facilitating paracrine effects.Methods and ResultsHuman mesenchymal stem cells (hMSC) were encapsulated in alginate and attached to the heart with a hydrogel patch in a rat myocardial infarction (MI) model. Cells were tracked using bioluminescence (BLI) and cardiac function measured by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR). Microvasculature was quantified using von Willebrand factor staining and scar measured by Masson's Trichrome. Post‐MI ejection fraction by CMR was greatly improved in encapsulated hMSC‐treated animals (MI: 34±3%, MI+Gel: 35±3%, MI+Gel+hMSC: 39±2%, MI+Gel+encapsulated hMSC: 56±1%; n=4 per group; P<0.01). Data represent mean±SEM. By TTE, encapsulated hMSC‐treated animals had improved fractional shortening. Longitudinal BLI showed greatest hMSC retention when the cells were encapsulated (P<0.05). Scar size at 28 days was significantly reduced in encapsulated hMSC‐treated animals (MI: 12±1%, n=8; MI+Gel: 14±2%, n=7; MI+Gel+hMSC: 14±1%, n=7; MI+Gel+encapsulated hMSC: 7±1%, n=6; P<0.05). There was a large increase in microvascular density in the peri‐infarct area (MI: 121±10, n=7; MI+Gel: 153±26, n=5; MI+Gel+hMSC: 198±18, n=7; MI+Gel+encapsulated hMSC: 828±56 vessels/mm2, n=6; P<0.01).ConclusionsAlginate encapsulation improved retention of hMSCs and facilitated paracrine effects such as increased peri‐infarct microvasculature and decreased scar. Encapsulation of MSCs improved cardiac function post‐MI and represents a new, translatable strategy for optimization of regenerative therapies for cardiovascular diseases.

Recent advances in human allogeneic islet transplantation have established b -cell replacement therapy as a potentially viable treatment option for individuals afflicted with Type 1 diabetes. Two recent successes, one involving neonatal porcine islet xenografts transplanted into diabetic rhesus macaques treated with a costimulation blockade-based regimen and the other involving diabetic cynomolgus monkeys transplanted with adult porcine islet xenografts treated with an alternative multidrug immunosuppressive regimen have demonstrated the feasibility of porcine islet xenotransplantation in nonhuman primate models. In the current study, we assessed whether transplantation of adult porcine islet xenografts into pancreatectomized macaques, under the cover of a costimulation blockade-based immunosuppressive regimen (CD28 and CD154 blockade), could correct hyperglycemia. Our findings suggest that the adult porcine islets transplanted into rhesus macaques receiving a costimulation blockade-based regimen are not uniformly subject to hyperacute rejection, can engraft (2/5 recipients), and have the potential to provide sustained normoglycemia. These results provide further evidence to suggest that porcine islet xenotransplantation may be an attainable strategy to alleviate the islet supply crisis that is one of the principal obstacles to large-scale application of islet replacement therapy in the treatment of Type 1 diabetes.

Microencapsulated API restored normoglycemia for more than 1 year in spontaneously diabetic NODs given dual CoB. To our knowledge, this is the first study to document long-term normalized HbA1c, porcine C peptide, and near normal glucose tolerance in immunosuppressed diabetic NOD mice transplanted intraperitoneally with microencapsulated API. Our study suggests that transplantation of microencapsulated porcine islet xenografts may be a future treatment for patients with type 1 diabetes mellitus.

Stem cell-based therapies hold great promise as a clinically viable approach for vascular regeneration. Preclinical studies have been very encouraging and early clinical trials have suggested favourable outcomes. However, significant challenges remain in terms of optimizing cell retention and maintenance of the paracrine effects of implanted cells. To address these issues, we have proposed the use of a cellular encapsulation approach to enhance vascular regeneration. We contained human mesenchymal stem cells (hMSCs) in biocompatible alginate microcapsules for therapeutic treatment in the setting of murine hindlimb ischaemia. This approach supported the paracrine pro-angiogenic activity of hMSCs, prevented incorporation of hMSCs into the host tissue and markedly enhanced their therapeutic effect. While injection of non-encapsulated hMSCs resulted in a 22 ± 10% increase in vascular density and no increase in perfusion, treatment with encapsulated hMSCs resulted in a 70 ± 8% increase in vascular density and 21 ± 7% increase in perfusion. The described cellular encapsulation strategy may help to better define the mechanisms responsible for the beneficial effects of cell-based therapies and provide a therapeutic strategy for inducing vascular growth in the adult. As hMSCs are relatively easy to isolate from patients, and alginate is biocompatible and already used in clinical applications, therapeutic cell encapsulation for vascular repair represents a highly translatable platform for cell-based therapy in humans.

No abstract