Protection of Encapsulated Human Islets Implanted Without Immunosuppression in Patients with Type I or Type II Diabetes in Nondiabetic Control Subjects

Dw, Scharp; Swanson, C. J.; Olack, Barbara; Latta, Paul; Hegre, Orion D.; Doherty, Edel; Gentile, Fabrizio; Flavin, Karen; M, Ansara; Lacy, Paul E.

doi:10.1097/00019616-199501000-00017

Cited by 29 publications

(31 citation statements)

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“…Implantation of a human islets-encapsulated permselective hollow fiber membrane into animals [26] and patients [27] has been applied for treatment of diabetes. Cells in encapsulated islets secreted insulin to normalize blood glucose levels in implanted receipts [27]. These results suggest that hollow fiber membranes served as immunoisolators that enhanced the survival of implanted human cells without rejection by receipt immune systems.…”

Section: Discussionmentioning

confidence: 99%

Bioengineering a humanized acne microenvironment model: Proteomics analysis of host responses to Propionibacterium acnes infection in vivo

et al. 2008

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Acne is a human disease of the sebaceous hair follicle. Unlike humans, most animals produce little or no triglycerides in hair follicles to harbor Propionibacterium acnes a fact that has encumbered the development of novel treatments for acne lesions. Although genetic mutant mice with acne-like skins have been used for screening anti-acne drugs, the mice generally have deficits in immune system that turns out to be inappropriate to generate antibodies for developing acne vaccines. Here, we employed a bioengineering approach using a tissue chamber integrated with a dermis-based celltrapped system (DBCTS) to mimic the in vivo microenvironment of acne lesions. Human sebocyte cell lines were grown in DBCTS as a scaffold and inserted into a perforated tissue chamber. After implantation of a tissue chamber bearing human sebocytes into ICR mice, P. acnes or PBS was injected into a tissue chamber to induce host immune response. Infiltrated cells such as neutrophils and macrophages were detectable in tissue chamber fluids. In addition, a proinflammatory cytokine macrophage-inflammatory protein-2 (MIP-2) was elevated after P. acnes injection. In tissue chamber fluids, 13 proteins including secreted proteins and cell matrix derived from mouse, human cells or P. acnes were identified by proteomics using isotope-coded protein label (ICPL) coupled to nano-LC-MS analysis. After P. acnes infection, four proteins including fibrinogen, α polypeptide, fibrinogen β chain, S100A9, and serine protease inhibitor A3K showed altered concentrations in the mimicked acne microenvironment. The bioengineered acne model thus provides an in vivo microenvironment to study the interaction of host with P. acnes and offers a unique set-up for screening novel anti-acne drugs and vaccines.

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Section: Discussionmentioning

confidence: 99%

Bioengineering a humanized acne microenvironment model: Proteomics analysis of host responses to Propionibacterium acnes infection in vivo

et al. 2008

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“…This concept is applied in several experimental models of xenotransplantation: such a strategy was efficient for pancreatic islets in mice [33] or for hepatocytes in rabbits [34]. In humans, some data are available demonstrating that HF protects human allogeneic islets [35] or porcine hepatocytes from rejection. Immunoisolation is also efficient in gene therapy with non-autologous engineered cells.…”

Section: Discussionmentioning

confidence: 99%

Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA)

Bessis

Honiger

Damotte

et al. 1999

Clinical and Experimental Immunology

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SUMMARYA strategy of gene therapy using IL-4 or IL-13 xenogeneic transfected cells encapsulated into permeable hollow fibres (HF) was used to treat CIA. Hydrogel-based hollow fibres were obtained from AN-69 copolymer, already known for its biocompatibility and tolerance in rodents. Permeability to IL-4 and lack of cell leakage from the fibres were ascertained in vitro and in vivo. Chinese hamster ovary (CHO) fibroblasts transfected with mouse IL-4 gene were encapsulated in HF (6·25 × 10 5 cells/HF). IL-4 was detected in vitro in the culture supernatant of filled fibres for at least 19 days. IL-4 or IL-13 transfected CHO cells encapsulated in HF were implanted in the peritoneum of mice on days 11-13 after immunization with type II collagen. Control mice were treated with fibre containing CHO cells transfected with b-galactosidase (bgal) gene; a positive control group consisted of mice treated by subcutaneous injection of 10 6 cells on days 10 and 25. Mice were monitored for signs of arthritis by observers unaware of the status of animals. Results of these experiments indicate that severity of the articular disease was significantly reduced in the groups of mice treated with CHO/IL-4 or CHO/IL-13 cells encapsulated in HF, compared with control groups receiving CHO/bgal cells encapsulated in HF. Histological analysis confirmed these data and extended them to a better inhibitory effect of encapsulated cells compared with free cells on inflammatory and destructive joint disease. Moreover, such long-term treatment with HF was well tolerated; macroscopic and histological aspects of peritoneal cavity were moderately inflammatory. Thus, our results may have important implications for clinical use of gene transfected cells as therapeutic agents in the treatment of autoimmune diseases.

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“…Subcutaneous islet transplant was performed in humans as early as 1994. Macroencapsulated islets harvested 2 weeks after implantation in diabetic or control patients without immunosuppression showed β-cell survival and glucose-dependent insulin secretion 46 . A pilot clinical study investigating the survival of microencapsulated islets within a prosthesis anastomosed to blood vessels reported that one of two transplanted patients showed transient insulin independence (both showed positive serum Cpeptide) 47 .…”

Section: Optimal Site For Islet Implantationmentioning

confidence: 96%

Optimal implantation site for pancreatic islet transplantation

Merani

Toso

Emamaullee

et al. 2008

British Journal of Surgery

229

173

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Protection of Encapsulated Human Islets Implanted Without Immunosuppression in Patients with Type I or Type II Diabetes in Nondiabetic Control Subjects

Cited by 29 publications

References 0 publications

Bioengineering a humanized acne microenvironment model: Proteomics analysis of host responses to Propionibacterium acnes infection in vivo

Bioengineering a humanized acne microenvironment model: Proteomics analysis of host responses to Propionibacterium acnes infection in vivo

Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA)

Optimal implantation site for pancreatic islet transplantation

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