异种胰岛移植中供体猪的筛选: 现状与进展

Zhu, Haitao; Yu, Long-Chuan; Lyu, Yi; Wang, Bo

doi:10.1631/jzus.b1400120

Cited by 23 publications

(39 citation statements)

References 87 publications

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“…Compared with other variables such as gender and body-weight, donor age seems to have a greater impact on islet size, yield, and functionality (Dufrane et al, 2005;Bottino et al, 2007;Kim et al, 2009). Neonatal pig pancreatic cell clusters (NPCCs) provide additional advantages over adult pig islets (APIs), such as their ease of isolation and purification, resistance to ischemia and inflammation during preparation, low cost, and low level of T-cell response (Nagaraju et al, 2015;Zhu et al, 2014a). After implantation, encapsulated immature pig islets, including NPCCs and fetal pig islet-like cell clusters (FPICCs), can proliferate and differentiate into mature β-cell masses and show excellent metabolic control in vivo (Omer et al, 2003b;Foster et al, 2007).…”

Section: Sources Of Pig Isletsmentioning

confidence: 99%

“…Nevertheless, the primary obstacle is that the cell density in this device needs to be quite low to ensure an adequate oxygen supply. This indicates that if large numbers of pig islets (25 000-100 000 IEQs/kg) are required to achieve insulin independence in diabetic NHPs (Hering et al, 2006;Casu et al, 2008;van der Windt et al, 2009;Thompson et al, 2011a;Zhu et al, 2014a), numerous or larger devices must be implanted. However, it is impossible to find a suitable surgical site to accommodate such macrodevices.…”

Section: Current Approachesmentioning

confidence: 99%

“…Due to a shortage of human donors, the sourcing of xenogenic islets from pig donors has emerged as an alternative strategy for transplantation. The pig is considered as the suitable islet donor candidate with advantages of the structural similarity between the insulin of pigs and humans, the lack of amyloid formation, resistance to recurrent autoimmunity, and feasibility for genetic immunomodulation (Koulmanda et al, 2003;Yonekawa et al, 2005;Potter et al, 2010;Wynyard et al, 2014;Zhu et al, 2014a;2014b). Recently, the demonstration of sustained diabetes reversal and prolonged survival of islet grafts (from wild-type or genetically modified pigs) in immunosuppressed diabetic non-human primates (NHPs) (van der Windt et al, 2009;Thompson et al, 2011a;2011b;Bottino et al, 2014) has signified a major step in the advance of the use of pig islets as a promising cellular therapy for the treatment of T1DM.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of diabetes with encapsulated pig islets: an update on current developments

Zhu

Liu

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:The potential use of allogeneic islet transplantation in curing type 1 diabetes mellitus has been adequately demonstrated, but its large-scale application is limited by the short supply of donor islets and the need for sustained and heavy immunosuppressive therapy. Encapsulation of pig islets was therefore suggested with a view to providing a possible alternative source of islet grafts and avoiding chronic immunosuppression and associated adverse or toxic effects. Nevertheless, several vital elements should be taken into account before this therapy becomes a clinical reality, including cell sources, encapsulation approaches, and implantation sites. This paper provides a comprehensive review of xenotransplantation of encapsulated pig islets for the treatment of type 1 diabetes mellitus, including current research findings and suggestions for future studies.

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Section: Sources Of Pig Isletsmentioning

confidence: 99%

Section: Current Approachesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treatment of diabetes with encapsulated pig islets: an update on current developments

Zhu

Liu

et al. 2015

J. Zhejiang Univ. Sci. B

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“…The limited supply of suitable human donor pancreases from which to yield transplant‐grade islets curtails wider use of β‐cell replacement therapy. However, porcine islet surrogates with a physiology similar to humans are increasingly being considered for clinical application as the risks from porcine endogenous retroviruses can be eliminated . Although xeno‐rejection remains a major challenge, various immune‐isolation strategies using biomaterials are in development.…”

Section: Introductionmentioning

confidence: 99%

Rotational culture and integration with amniotic stem cells reduce porcine islet immunoreactivity in vitro and slow xeno‐rejection in a murine model of islet transplantation

Zafar

Lee

Paget

et al. 2019

Xenotransplantation

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Background Pre‐transplant modification of porcine islets may improve their suitability for clinical use in diabetes management by supporting graft function and reducing the potential for xeno‐rejection. The present study investigates intra‐graft incorporation of stem cells that secrete beta (β)‐cell trophic and immunomodulatory factors to preserve function and alter immune cell responsiveness to porcine islets. Methods Isolated porcine islets were maintained in a three‐dimensional rotational cell culture system (RCCS) to facilitate aggregation with human amniotic epithelial cells (AECs). Assembled islet constructs were assessed for functional integrity and ability to avoid xeno‐recognition by CD4+ T‐cells using mixed islet:lymphocyte reaction assays. To determine whether stem cell‐mediated modification of porcine islets provided a survival advantage over native islets, structural integrity was examined in a pig‐to‐mouse islet transplant model. Results Rotational cell culture system supported the formation of porcine islet:AEC aggregates with improved insulin‐secretory capacity compared to unmodified islets, whilst the xeno‐response of purified CD4+ T‐cells to AEC‐bearing grafts was significantly (P < 0.05) attenuated. Transplanted AEC‐bearing grafts demonstrated slower rejection in immune‐competent recipients compared to unmodified islets. Conclusions/interpretation Rotational culture enables pre‐transplant modification of porcine islets by integration with immunomodulatory stem cells capable of subduing xeno‐reactivity to CD4+ T‐cells. This reduces islet rejection and offers translational potential to widen availability and improve the clinical effectiveness of islet transplantation.

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“…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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异种胰岛移植中供体猪的筛选: 现状与进展

Cited by 23 publications

References 87 publications

Treatment of diabetes with encapsulated pig islets: an update on current developments

Treatment of diabetes with encapsulated pig islets: an update on current developments

Rotational culture and integration with amniotic stem cells reduce porcine islet immunoreactivity in vitro and slow xeno‐rejection in a murine model of islet transplantation

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

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