Hydroxymethylated polysulphone for islet macroencapsulation allows rapid diffusion of insulin but retains PERV

Petersen, Peter; Lembert, Nicolas; Zschocke, P.; Stenglein, Stephen; Planck, H.; Ammon, H. P. T.; Becker, H. D.

doi:10.1016/s0041-1345(01)02724-5

Cited by 15 publications

(9 citation statements)

References 6 publications

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“…In addition, the lack of PERV transmission is consistent with preliminary studies using encapsulated porcine islets from the same donor pigs where recipient monitoring was performed for up to 9-yr post-transplant [20] and explantation of viable cells was achieved after 19 months post-transplant [55]. It also is possible that the lack of evidence for PERV infection may be due to the encapsulation of the islet cells reducing the release of PERV given that the capsule pores are smaller than the virus [56,57]. However, for the NZ DPF herd, this point is likely invalid as infectivity studies using the supernatant of cultivated encapsulated cells, and the measured reverse transcriptase activity in this supernatant have always been negative [23,38,39].…”

Section: Discussionsupporting

confidence: 82%

Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand

Wynyard

Nathu

Garkavenko

et al. 2014

Xenotransplantation

208

249

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Background: Xenotransplantation using pig cells, tissues, or organs may be associated with the transmission of porcine microorganisms and the development of zoonoses. Among all porcine microorganisms porcine endogenous retroviruses (PERVs) represent a special risk because they are integrated in the genome of all pigs and able to infect human cells. In previous preclinical and retrospective clinical trials of xenotransplantation, no transmission of PERV was observed. The first clinical trial of (alginate-encapsulated) porcine islet cell transplantation in New Zealand, which was approved by the New Zealand Government as an open-label phase I/IIa safety/efficacy trial, offers the possibility to analyze microbiological safety in a prospective clinical study. Methods: Before the trial started, a multilevel testing strategy was used to screen for 26 microorganisms in donor pigs of the Auckland Island strain and the islet cell preparations used for treatment. Donor testing was performed using molecular methods including multiplex real-time PCR. Blood samples from 14 pig islet cell recipients were also investigated by molecular biological methods at weeks 1, 4, 8, 12, 24, and 52 post-transplant for the transmission of porcine microorganisms. Sera were also monitored at these time points for antibodies against PERVs. Results: Beginning in 2009, fourteen patients with severe unaware hypoglycemia were treated with one of four different dosages of alginate-encapsulated porcine islets ranging from 5000-20 000 islet equivalents delivered in a single dose. No transmission of either PERVs or other porcine microorganisms was detected by PCR and immunological methods. Conclusion: These findings support previous results and strongly indicate the safety of xenotransplantation as performed here.

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Section: Discussionsupporting

confidence: 82%

Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand

Wynyard

Nathu

Garkavenko

et al. 2014

Xenotransplantation

208

249

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“…PSU is focused on as a possible material for encapsulated islets because large amounts of insulin are absorbed by the PSU hollow fibers. Lembert et al [39,40] developed hydroxy-methylated PSU "macroencapsulated" islets which showed good insulin releasing function similar to naked islets while blocking endogenous retrovirus infection. Transplantation of their device also achieved normoglycemia in diabetic rats for over 1 mo [41] .…”

Section: Resultsmentioning

confidence: 99%

Encapsulated islets transplantation: Past, present and future

Sakata

Sumi²,

Yoshimatsu³

et al. 2012

WJGP

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Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient's immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient's immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.

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“…Other in vitro assays performed by the same team with highly hydroxylated PSU yielded even better results (67 ± 10 ng/mL × 90 min), although perfusion studies were never conducted for more than 4 days. These authors also reported no response could be observed from native PSU or PSU/PVP capillaries (Petersen et al, 2002).…”

Section: Performance Of Islets Of Langerhans and Their Use In A Bap Mmentioning

confidence: 92%

“…In other studies PSU was used for in vitro experiments to determine its immunoisolation ability against viruses (Petersen et al, , 2002.…”

Section: Introductionmentioning

confidence: 99%

Development of a polysulfone hollow fiber vascular bio-artificial pancreas device for in vitro studies

Silva¹,

Mateus²

2009

Journal of Biotechnology

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Hydroxymethylated polysulphone for islet macroencapsulation allows rapid diffusion of insulin but retains PERV

Cited by 15 publications

References 6 publications

Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand

Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand

Encapsulated islets transplantation: Past, present and future

Development of a polysulfone hollow fiber vascular bio-artificial pancreas device for in vitro studies

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