| Correlation of Released HMGB1 Levels with the Degree of Islet Damage in Mice and Humans and with the Outcomes of Islet Transplantation in Mice. | |
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MedLine Citation:
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PMID: 22546320 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Establishing reliable islet potency assay is a critical and unmet issue for clinical islet transplantation. Recently, we reported that islets contained high levels of high-mobility group box 1 (HMGB1) and damaged islets released HMGB1 in a mouse model. In this study, we hypothesized that the amount of released HMGB1 could reflect the degree of islet damage, and could predict the outcome of islet transplantation. Four groups of damaged mouse islets and three groups of damaged human islets were generated by hypoxic conditions. These islets were assessed by in vivo (transplantation) and in vitro (released HMGB1 levels, released Cpeptide levels, PI staining, TUNEL staining, ATP/DNA and glucose-stimulated insulin release test) assays. In addition, the ability of each assay to distinguish between non-cured (n=13) and cured (n=7) mice was assessed. The curative rates of STZ-diabetic mice after receiving control, hypoxia-3hr, hypoxia-6hr and hypoxia-24hr mouse islets were 100%, 40%, 0%, and 0%, respectively. Only amounts of released HMGB1 and ratio of PI staining significant increased according to the degree of damages in both human and mouse islets. In terms of predictability of curing diabetic mice, amounts of released HMGB1 showed the best sensitivity (100%), specificity (100%), positive (100%) and negative predictive values (100%) among all the assays. The amount of released HMGB1 reflected the degree of islet damage and correlated with the outcome of islet transplantation in mice. Hence, released HMGB1 levels from islets should be a useful marker to evaluate the potency of isolated islets. |
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Authors:
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Takeshi Itoh; Morihito Takita; Jeffrey A Sorelle; Masayuki Shimoda; Koji Sugimoto; Daisuke Chujo; Huanying Qin; Bashoo Naziruddin; Marlon F Levy; Shinichi Matsumoto |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-26 |
Journal Detail:
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Title: Cell transplantation Volume: - ISSN: 1555-3892 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-5-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9208854 Medline TA: Cell Transplant Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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