Long-Term Metabolic Control of Autoimmune Diabetes in Spontaneously Diabetic Nonobese Diabetic Mice by Nonvascularized Microencapsulated Adult Porcine Islets

Cheng, Hong; Tucker-Burden, Carol; Cauffiel, Sean M. D.; Barry, Adrienne K.; Iwakoshi, Neal N.; Weber, Collin J.; Safley, Susan A.

doi:10.1097/tp.0b013e3181abbfc1

Cited by 59 publications

(77 citation statements)

References 29 publications

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“…Calcium-alginate gels with 1.8% alginate are permeable to IgG (150 kDa) [50], hence most culture media additions will freely diffuse into the alginate beads, including BSA (66 kDa). Indeed, pancreatic islets have been shown to be viable and functioning in alginate gels over the lifespan of mice [51], indicating that diffusion restrictions of the material is not limiting to the viability and function of the encapsulated tissue. In this study, the similarities of expression of pancreatic markers in encapsulated and non-encapsulated samples indicate that there is no significant reduction in diffusion of relevant molecules to the encapsulated tissue.…”

Section: Alginate Matrices Do Not Stimulate Progenitor Maturation Intmentioning

confidence: 99%

Culture of hESC‐derived pancreatic progenitors in alginate‐based scaffolds

Formo

Cho

Vallier

et al. 2015

J Biomedical Materials Res

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The effect of alginate-based scaffolds with added basement membrane proteins on the in vitro development of hESC-derived pancreatic progenitors was investigated. Cell clusters were encapsulated in scaffolds containing the basement membrane proteins collagen IV, laminin, fibronectin, or extracellular matrix-derived peptides, and maintained in culture for up to 46 days. The cells remained viable throughout the experiment with no signs of central necrosis.Whereas non-encapsulated cells aggregated into larger clusters, some of which showed signs of morphological changes and tissue organization, the alginate matrix stabilized the cluster size and displayed more homogeneous cell morphologies, allowing culture for long periods of time. For all conditions tested, a stable or declining expression of insulin and PDX1 and an increase in glucagon and somatostatin over time indicated a progressive reduction in beta cellrelated gene expression. Alginate scaffolds can provide a chemically defined, xeno-free and easily scalable alternative for culture of pancreatic progenitors. Although no increase in insulin and PDX1 gene expression after alginate-immobilized cell culture was seen in this study, further optimization of the matrix physicochemical and biological properties and of the medium composition may still be a relevant strategy to promote the stabilization or maturation of stem cell-derived beta cells.

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Section: Alginate Matrices Do Not Stimulate Progenitor Maturation Intmentioning

confidence: 99%

Culture of hESC‐derived pancreatic progenitors in alginate‐based scaffolds

Formo

Cho

Vallier

et al. 2015

J Biomedical Materials Res

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“…According to Cui et al subsequent to graft retrieval and confi rmation of microcapsule structural integrity, histological evaluation demonstrated signifi cant PFO and islet necrosis in APIs. Upon further evaluation, eosinophils, macrophages, and to a lesser extent, CD4+ T-cells, CD8+ T-cells, B-cells and neutrophils were detected in the peritoneal fl uid [ 80 ]. Serum examined from these immune-competent mice had increased levels of circulating anti-porcine IgG relative to baseline values observed in the control group.…”

Section: Adult Porcine Islets [Apis]mentioning

confidence: 92%

“…The hypothesis that rejection was initiated despite no sign of microcapsule degradation hinges on antigenic small-molecule secretion by APIs. Islet antigens and other DAMPs can be detected by antibodies in the extracapsular space and activate peritoneal macrophages via F c receptor interactions [ 80 ]. In addition to capsule-permeable toxic mediators secreted by macrophages, in immunosuppressed mice, xenograft destruction was also reported to correlate with eosinophil recruitment, and a primarily humoral response [ 81 ].…”

Section: Adult Porcine Islets [Apis]mentioning

confidence: 99%

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials

Krishnan

Foster

et al. 2016

Cell Microencapsulation

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Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of signifi cant parameters of bioencapsulation device design and manufacture (i.e., purifi cation protocols, surface-modifi cation grafting techniques, alginate composition modifi cations) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specifi c pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defi ning characteristics of the response itself.

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“…Peritoneal mesothelial cells facilitate the induction and promotion of a strong innate immune reaction to antigen. Recently, studies of encapsulated pig islets transplanted into mice reported that the biocompatibility was improved and the survival of encapsulated pig islet transplants was prolonged by the inhibition of macrophage and lymphocyte stimulation [27]. Therefore, we attempted to evaluate a site that would be less immunoreactive for implantation of islet xenograft microcapsules, and that would also avoid the need for immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Poloxamer 188 as a Supplement to Barium Cross-Linked Ultra-High Viscosity Alginate for Immunoisolation of Transplanted Islet Cells

Mettler¹,

Zimmermann²,

Hansen³

et al. 2015

Metabolomics

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elastic gels with high permeability compared to alginates with a high content of mannuronic acid [5]. Therefore, the M:G ratio, length of polymeric chains, and ratio of homologous to heterologous chains must be carefully tuned to optimize the microcapsules [6].A lack of standardization and information from manufacturers about the composition of the alginate (e.g., molecular weight, content, and ratio of D-mannuronic acid and L-guluronic acid) is a major problem for encapsulation experiments; this knowledge is of enormous importance for understanding the physico-chemical characteristics and hence biocompatibility of the alginate. Ba 2+ -gelled capsules comprised of 1:1 mixtures of UHV alginates from the closely related species Lessonia nigrescens and Lessonia trabeculata meet the demands of high stability and flexibility (UHV: 35% M and 65% G) [7].The aims of the current study were 1) to improve the physical features of barium cross-linked UHV alginate by the addition of Poloxamer 188 (P188) as a detergent, and 2) to establish the muscle as a novel transplantation site.Poloxamer is comprised of ABA-type block polymers that consist of a central, hydrophobic block of polypropylene oxide that is edged by two hydrophilic blocks of polyethylene oxide. Poloxamer 188 (P188),

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Long-Term Metabolic Control of Autoimmune Diabetes in Spontaneously Diabetic Nonobese Diabetic Mice by Nonvascularized Microencapsulated Adult Porcine Islets

Cited by 59 publications

References 29 publications

Culture of hESC‐derived pancreatic progenitors in alginate‐based scaffolds

Culture of hESC‐derived pancreatic progenitors in alginate‐based scaffolds

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials

Poloxamer 188 as a Supplement to Barium Cross-Linked Ultra-High Viscosity Alginate for Immunoisolation of Transplanted Islet Cells

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