Background Stem 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 Results Human mesenchymal stem ( hMSC ) were encapsulated alginate attached the heart with a hydrogel patch rat myocardial infarction MI model. Cells tracked using bioluminescence BLI function measured by transthoracic...

Nonhuman primates (NHPs) have been widely used in different porcine xenograft procedures inevitably resulting exposure to endogenous retrovirus (PERV). Surveillance for PERV infection these NHPs may provide information on the risks of cross-species transmission PERV, particularly recipients vascularized organ xenografts whom data from human clinical trials is unavailable.We tested 21 Old World and 2 New exposed a variety evidence infection. These included six baboon pig hearts, bonnet...

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 suggested favourable outcomes. However, significant challenges remain in terms of optimizing cell retention maintenance the paracrine effects implanted cells. To address these issues, we proposed use cellular encapsulation to enhance We contained human mesenchymal stem cells (hMSCs) biocompatible alginate...

Abstract Background Xenogeneic donors would provide an unlimited source of islets for the treatment type 1 diabetes (T1D). The goal this study was to assess function microencapsulated adult porcine ( API s) transplanted ip in streptozotocin STZ )‐diabetic non‐human primates NHP given targeted immunosuppression. Methods s were encapsulated in: (a) single barium‐gelled alginate capsules or (b) double with inner, islet‐containing compartment and a durable, biocompatible outer layer....

If alginate microcapsules are to be used clinically for therapeutic cell transplants, capsule formulations must designed enhance optimal biocompatibility and immune acceptance.Microcapsules were generated using highly purified, endotoxin-free, ultra-low viscosity, high mannuronic acid alginate. The capsules differed with respect gelling cation (50 mM barium or 100 calcium), concentration (2.0% 3.3%), density (homogeneous inhomogeneous), the presence absence poly-L-lysine (PLL) coating. Four...

Background. The long-term metabolic function of microencapsulated xenogeneic adult porcine islets (API) was assessed in a murine model type 1 diabetes mellitus. Methods. API were encapsulated barium-gelled alginate and transplanted intraperitoneally diabetic nonobese (NOD) mice given no immunosuppression or costimulatory blockade (CoB; CTLA4-Ig+anti-CD154 mAb). Control received nonencapsulated under the kidney capsule. Graft monitored by measurement random blood glucose levels, serum...

Using a murine model, we investigated the role of bacterial exotoxin listeriolysin O (LLO) in cellular immunity to Listeria monocytogenes. A correlation between LLO production by infecting bacteria and generation protective virulent LLO-producing was noted. isogeneic hemolysin (Hly+ or Hly-) strains L. monocytogenes, demonstrated that is required elicit T cells reactive both bacteria-associated Ag secreted molecule as measured IL-2 vitro. Distinct sets specific for largely nonoverlapping...

Background. Transplantation of human islets has been successful clinically. Since are scarce, we studying microencapsulated porcine islet xenografts in nonobese diabetic (NOD) mice. We have evaluated the cellular immune response NOD mice with and without dual costimulatory blockade. Methods. Alginate-poly-L-lysine-encapsulated adult were transplanted i.p. untreated NODs treated CTLA4-Ig to block CD28/B7 anti-CD154 mAb inhibit CD40/CD40-ligand interactions. Groups sacrificed on subsequent...

Using a Salmonella vaccine-Listeria infection model of intracellular infection, we studied the capacity an attenuated strain carrying T-cell epitopes listeriolysin (LLO) L. monocytogenes to elicit epitope-specific responses. Class II (LLO 215–226) or class I 91–99) MHC-restricted LLO were inserted within central, hypervariable domain flagellin protein ΔaroA dublin strain. T cells from Listeria-immunized mice activated by lysates heat-killed preparations construct expressing 215–226 epitope,...

Abstract Background Adult porcine islets ( API s) constitute a promising alternative to human in treating type 1 diabetes. The intrahepatic site has been used preclinical primate studies of xenografts; however, an estimated two‐thirds donor are destroyed after intraportal infusion due number factors, including the instant blood‐mediated inflammatory reaction IBMIR ), immunosuppressant toxicity, and poor reestablishment extracellular matrix connections. Intraperitoneal (ip) transplantation...

Abstract Background Our goal was to improve islet transplantation as a therapy for patients with type I diabetes mellitus. Because human donor islets are scarce, we studying xenografts in the diabetic NOD mouse model. We hypothesize that optimal xenoislet survival will be achieved by combination of immunoisolation recipient immunosuppression. and others have studied adult neonatal porcine sources tissue microencapsulated xenografts, but believe it is also advantageous consider using from...

The cell-mediated immune response to Listeria monocytogenes has been well characterized in the mouse. Listeriolysin O (LLO) is a major antigen murine T-cell recognition of L. monocytogenes. In this study, we show that LLO also recognized by human TcR alpha beta T cells and gamma delta cells. Human peripheral blood mononuclear (PBMC) cultured vitro with live listeriae then expanded interleukin 2 were shown respond purified LLO. generation LLO-responsive was dependent on use bacteria during...

SUMMARY Parathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection parathyroid tumours. Because is also expressed in normal parathyroids and other endocrine cells (adrenal islet), we hypothesized that tumours might contribute directly hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, chromogranin-A (an...

We demonstrate conclusively that the bacterial exotoxin listeriolysin O (LLO) is a target Ag for eliciting CD4+ T cell responses following infection with Listeria monocytogenes. The minimal I-Ek-restricted immunodominant epitope was identified as peptide 215-226 (p215-226). Most LLO-specific hybridomas recognized p203-226, p208-226, p215-226, and p215-234, although each exhibited characteristic pattern of preferential reactivity. One hybridoma (IIIC5) reacted to p203-226 but not p208-226 or...

The hemolysin, listeriolysin 0 (LLO), produced by Listeria monocytogenes is both a virulence factor and an immunodominant Ag. In this study, we investigated how the lytic activity of LLO effects context presentation two known epitopes either class I or II MHC molecules. T cell hybridomas were used to monitor each peptide/MHC ligand. APCs infected with strains expressing hemolytic strongly presented epitope; however, ligand was not well cells nonhemolytic Listeria. contrast, there almost no...

The efficacy of pancreatic islet transplants in correcting hyperglycemia and slowing the progression complications diabetics has been confirmed by many experimental clinical studies. Unfortunately, availability human islets is extremely limited and, therefore, treatment large numbers diabetic patients will almost certainly require either use harvested from animals (xenografts) or insulin-secreting genetically modified cells animal origin. There currently no effective regimen which allow...

Pancreatic islet transplantation improves metabolic control and prevents complications in patients with brittle type 1 diabetes (T1D). However, chronic immunosuppression is required to prevent allograft rejection recurrence of autoimmunity. Islet encapsulation may eliminate the need for immunosuppression. Here, we analyzed parallel two microencapsulation platforms that provided long-term reversal preclinical T1D models, alginate single double capsules versus polyethylene glycol conformal...

Our goal is to develop effective islet xenografts for treating human diabetes. We have studied microencapsulated neonatal porcine cell clusters (ICCs) transplanted intraperitoneally in spontaneously diabetic NOD mice, where they function maintain normoglycemia the autoimmune host. Nonencapsulated ICCs functioned 4.5 ± 0.5 days before being rejected; encapsulation prolonged graft 17 2 days. CTLA4-Ig treatment did not enhance survival of nonencapsulated ICCs. However, significantly extended...

Abstract Background Our goal was to identify clinically relevant immunotherapies that synergize with microencapsulation protect adult porcine islet (API) xenografts in diabetic NOD mice. We have shown previously dual costimulatory blockade (CTLA4‐Ig plus anti‐CD154 mAb) combined encapsulation protects APIs long‐term Since no mAbs currently are approved for use humans, we tested the efficacy of other targeted immunosuppression regimens might be used patients receiving encapsulated islets....