Current status of islet xenotransplantation

Park, Chung Gyu; Bottino, Rita; Hawthorne, Wayne J.

doi:10.1016/j.ijsu.2015.07.703

Cited by 80 publications

(73 citation statements)

References 33 publications

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“…The diabetic non-human primate model has been used extensively to show the efficacy of transplanted adult and neonatal porcine islets with variable degrees of success in a number of preclinical studies as reviewed here [1][2][3]. Naturally, preserving implanted islets from the host immune response was central in most of these studies.…”

Section: Introductionmentioning

confidence: 99%

Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species

Mourad

Gianello

2017

Curr Transpl Rep

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Purpose of Review Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation. Recent Findings In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation. Moreover, combining multiple modifications is possible today thanks to new, improved genomic editing tools. Summary Genetic modification of large animals, pigs in particular, has come a long way during the last decade. These modifications can help minimize immunological and physiological incompatibilities between porcine and human cells, thus allowing for better tolerance and function of xenocells.

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Section: Introductionmentioning

confidence: 99%

Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species

Mourad

Gianello

2017

Curr Transpl Rep

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“…The generalized strategies to introduce porcine genetic modification are knocking down or knocking out certain genes for polysaccharide antigens, e.g., α-Gal, knocking in human complement regulatory proteins, coagulation and cellular immune response regulatory proteins, respectively, or combinations of the above genetic modifications. Technical speed development for genetically engineering modified pigs provides another approach to realize clinical islet xenotransplantation [48].…”

Section: Livermentioning

confidence: 99%

Xenotransplantation for Islets from Clinical Side

Wang¹,

Liang²,

Nie³

et al. 2017

Xenotransplantation - New Insights

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Islet transplantation can eliminate severe hypoglycemia symptoms caused by conventional treatment, and has the advantages of less trauma and complications, which is considered as the most promising treatment for type 1 diabetes mellitus (T1DM). Regulatory guidance is needed for a standard pig source. In section 1, the regulation of medical grade designed pathogen free (DPF) donor pig for clinical xenotransplantation consists of five parts: genetic quality control, microbiological surveillance, formula feeds, specification of pathological diagnosis, and requirements of environment and housing facilities. In section 2, we present the current approach and progress in pig donor selecting, pancreatic digestion, isolation and preparation of porcine islet grafts, identification and quality assessment of final islet product in clinical trials. The liver is currently the most preferred site for islet transplantation, even though it is far from ideal. A large number of alternative sites have been used for islet transplantation in experimental animal models to provide improved engraftment and long-term survival. In Section 3, we introduce some commonly used sites in xenotransplantation. The benefits and drawbacks of each parameter above are discussed in an attempt to decide which is the most suitable for clinical use and to direct future research.

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“…There is still a debate on the best source of the porcine islets, but at least adult, neonatal, and embryonic pancreata have been shown to be efficient for controlling hyperglycemia in higher mammals including NHPs [19,20,33]. Because advantages and disadvantages of using each islet source have been repeatedly discussed elsewhere [30,34], here we focus on adult porcine islets from DPF miniature pigs. Our group had obtained an SPF miniature pig strain from the University of Chicago in 2004 and have been breeding and maintaining a closed herd in a SPF barrier facility.…”

Section: History and Characteristics Of Snu Miniature Pigsmentioning

confidence: 99%

“…Because other related topics including encapsulated pig islets, islet sources, immunosuppression regimen, and overall results from several pig-to-NHP islet xenotransplantation have been elegantly described elsewhere [15,[29][30][31][32], here we will focus on the above themes while briefly reviewing past and current status of each area.…”

Section: Introductionmentioning

confidence: 99%

Pig-to-Nonhuman Primate (NHP) Naked Islet Xenotransplantation

Shin¹,

Kim²,

Min³

et al. 2017

Xenotransplantation - New Insights

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Islet transplantation is an established therapy for selected type 1 diabetes (T1D) patients with severe hypoglycemic unawareness and glycemic liability despite of insulin treatment. However, the donor organ is limited. Porcine islets are the best alternative source to overcome this limitation, and pig-to-nonhuman primate (NHP) naked islet xenotransplantation studies are being performed worldwide. Several studies including our own have presented successful proof-of-concept results based on immunosuppression regimen including the anti-CD154 monoclonal antibody. Particularly, long-term control of diabetes by adult porcine islet transplantation has been demonstrated in five consecutive monkeys, and the longest survival was ~1000 days after transplantation. Currently, pig-to-NHP islet xenotransplantation based on clinically applicable immunosuppression regimen is being pursued. In this chapter, we will describe all the procedures of pigto-NHP naked islet xenotransplantation: (1) the porcine islet isolation from designated pathogen-free (DPF) miniature pigs, (2) diabetes induction in monkeys, (3) transplantation procedure via the portal vein, (4) immune monitoring comprising humoral and cellular immunity after porcine islet transplantation, and finally (5) liver biopsy and subsequent immunohistochemical procedure in detail.

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Current status of islet xenotransplantation

Cited by 80 publications

References 33 publications

Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species

Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species

Xenotransplantation for Islets from Clinical Side

Pig-to-Nonhuman Primate (NHP) Naked Islet Xenotransplantation

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