Impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome

Daria Zorzi, Tammy Phan, Marco Sequi, Yong Lin, Daniel H. Freeman, Luca Cicalese, Cristiana Rastellini

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 µm; medium 150–300 mm; small, <150 µm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.

    Original languageEnglish (US)
    Pages (from-to)11-23
    Number of pages13
    JournalCell Transplantation
    Volume24
    Issue number1
    DOIs
    StatePublished - 2015

    Fingerprint

    Islets of Langerhans Transplantation
    Immunosuppression
    Pancreas
    Transplants
    Transplantation
    Medical problems
    Control Groups
    Animals

    Keywords

    • Islet engraftment
    • Islet fragmentation
    • Islet functionality
    • Islet overdigestion
    • Islet size
    • Murine model islet transplant

    ASJC Scopus subject areas

    • Biomedical Engineering
    • Cell Biology
    • Transplantation

    Cite this

    Impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome. / Zorzi, Daria; Phan, Tammy; Sequi, Marco; Lin, Yong; Freeman, Daniel H.; Cicalese, Luca; Rastellini, Cristiana.

    In: Cell Transplantation, Vol. 24, No. 1, 2015, p. 11-23.

    Research output: Contribution to journalArticle

    Zorzi, Daria ; Phan, Tammy ; Sequi, Marco ; Lin, Yong ; Freeman, Daniel H. ; Cicalese, Luca ; Rastellini, Cristiana. / Impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome. In: Cell Transplantation. 2015 ; Vol. 24, No. 1. pp. 11-23.
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    AB - Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 µm; medium 150–300 mm; small, <150 µm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.

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