Islet Transplantation Using Donors After Cardiac Death: Report of the Japan Islet Transplantation Registry

Saito, Takuro; Gotoh, Mitsukazu; Satoh, Susumu; Üemoto, Shinji; Kenmochi, Takashi; Itoh, Taiki; Kuroda, Yoshikazu; Yasunami, Y; Matsumoto, S.; Teraoka, Satoshi

doi:10.1097/tp.0b013e3181ecb044

Cited by 52 publications

(28 citation statements)

References 36 publications

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“…To match the demand for regenerative medicine it is necessary to find an available and unlimited reservoir of hMSCs. Bone marrow transplantation [9] as well as pancreatic islets [22] from cadaveric donors have been reported in several studies as a clinical reality. Asystolic, cadaver donors are utilized to provide multiple organs and tissues for transplants, and stem cell retrieval from these sources could represent an original and noteworthy choice.…”

Section: Discussionmentioning

confidence: 99%

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

Valente

Alviano²,

Ciavarella

et al. 2014

Stem Cell Res Ther

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IntroductionRegenerative medicine challenges researchers to find noncontroversial, safe and abundant stem cell sources. In this context, harvesting from asystolic donors could represent an innovative and unlimited reservoir of different stem cells. In this study, cadaveric vascular tissues were established as an alternative source of human cadaver mesenchymal stromal/stem cells (hC-MSCs). We reported the successful cell isolation from postmortem arterial segments stored in a tissue-banking facility for at least 5 years.MethodsAfter thawing, hC-MSCs were isolated with a high efficiency (12 × 106) and characterized with flow cytometry, immunofluorescence, molecular and ultrastructural approaches.ResultsIn early passages, hC-MSCs were clonogenic, highly proliferative and expressed mesenchymal (CD44, CD73, CD90, CD105, HLA-G), stemness (Stro-1, Oct-4, Notch-1), pericyte (CD146, PDGFR-β, NG2) and neuronal (Nestin) markers; hematopoietic and vascular markers were negative. These cells had colony and spheroid-forming abilities, multipotency for their potential to differentiate in multiple mesengenic lineages and immunosuppressive activity to counteract proliferation of phytohemagglutinin-stimulated blood mononuclear cells.ConclusionsThe efficient procurement of stem cells from cadaveric sources, as postmortem vascular tissues, demonstrates that such cells can survive to prolonged ischemic insult, anoxia, freezing and dehydration injuries, thus paving the way for a scientific revolution where cadaver stromal/stem cells could effectively treat patients demanding cell therapies.

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Section: Discussionmentioning

confidence: 99%

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

Valente

Alviano²,

Ciavarella

et al. 2014

Stem Cell Res Ther

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“…To date, the success of DCD islets in the context of clinical islet transplantation has been evaluated at few single centers worldwide, with limited long-term successful outcomes. [13][14][15] The necessity to establish preclinical models evaluating the utility of DCD islets could provide insights into their clinical application. Herein, we sought to establish a murine DCD model and evaluate its efficacy in a marginal, syngeneic islet transplant model, as well as determine if supplementation with a novel MnP during organ procurement, islet isolation and brief culture could improve DCD islet transplant function.…”

Section: Discussionmentioning

confidence: 99%

A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model

Bruni

Pepper

Gala-López

et al. 2016

Islets

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(2016) A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model, Islets, 8:4, e1190058, DOI: 10.1080/19382014.2016 ABSTRACTIslet transplantation is a highly effective treatment for stabilizing glycemic control for select patients with type-1 diabetes. Despite improvements to clinical transplantation, single-donor transplant success has been hard to achieve routinely, necessitating increasing demands on viable organ availability. Donation after circulatory death (DCD) may be an alternative option to increase organ availability however, these organs tend to be more compromised. The use of metalloporphyrin antiinflammatory and antioxidant (MnP) compounds previously demonstrated improved in vivo islet function in preclinical islet transplantation. However, the administration of MnP (BMX-001) in a DCD islet isolation and transplantation model has yet to be established. In this study, murine donors were subjected to a 15-min warm ischemic (WI) period prior to isolation and culture with or without MnP. Subsequent to one-hour culture, islets were assessed for in vitro viability and in vivo function. A 15-minute WI period significantly reduced islet yield, regardless of MnP-treatment relative to yields from standard isolation. MnP-treated islets did not improve islet viability compared to DCD islets alone. MnP-treatment did significantly reduce the presence of extracellular reactive oxygen species (ROS) (p < 0 .05). Marginal, syngeneic islets (200 islets) transplanted under the renal capsule exhibited similar in vivo outcomes regardless of WI or MnP-treatment. DCD islet grafts harvested 7 d post-transplant exhibited sustained TNF-a and IL-10, while MnP-treated islet-bearing grafts demonstrated reduced IL-10 levels. Taken together, 15-minute WI in murine islet isolation significantly impairs islet yield. DCD islets do indeed demonstrate in vivo function, though MnP therapy was unable to improve viability and engraftment outcomes.

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“…Islet cell transplantation is a treatment option that it is hoped will improve blood glucose levels, resulting in an improved prognosis for patients with diabetes mellitus [78,79]. Technologies for pancreatic islet cell transplantation using delivery vectors have been developed.…”

Section: Islet Cell Transplantationmentioning

confidence: 99%

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

Ookawara

Ishibashi

et al. 2017

Nano Reviews & Experiments

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Gene therapy that targets the pancreas and intestines with delivery systems using nano-sized carriers such as viral and non-viral vectors could improve the control of blood glucose levels, resulting in an improved prognosis for patients with diabetes mellitus. Allogenic pancreatic islet cell transplantations using such delivery systems have been developed as therapeutic options for diabetes mellitus. This review focuses on transgenes and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus.

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Islet Transplantation Using Donors After Cardiac Death: Report of the Japan Islet Transplantation Registry

Cited by 52 publications

References 36 publications

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

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