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    Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates

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    Preliminary_Studies_of_the_Imp ...
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    Author
    Sremac, Marinko
    Lei, Ji
    Penson, Madeline F E
    Schuetz, Christian
    Lakey, Jonathan R T
    Papas, Klearchos K
    Varde, Pushkar S
    Hering, Bernhard
    de Vos, Paul
    Brauns, Timothy
    Markmann, James
    Poznansky, Mark C
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    Affiliation
    Univ Arizona, Dept Surg, Inst Cellular Transplantat
    Issue Date
    2019-04-15
    
    Metadata
    Show full item record
    Publisher
    LIPPINCOTT WILLIAMS & WILKINS
    Citation
    Sremac, M., Lei, J., Penson, M. F., Schuetz, C., Lakey, J. R., Papas, K. K., ... & Poznansky, M. C. (2019). Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates. Transplantation direct, 5(5).
    Journal
    TRANSPLANTATION DIRECT
    Rights
    Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Background. We previously demonstrated that the incorporation of the chemokine CXCL12 into alginate microbeads supported long-term survival of microencapsulated auto-, allo-, and xenogeneic islets in murine models of diabetes without systemic immune suppression. The purpose of this study was to test whether CXCL12 could abrogate foreign body responses (FBRs) against alginate microbeads which were empty or contained autologous islets in healthy nonhuman primates (NHPs; n = 4). Methods. Two NHPs received intraperitoneal implants of 400000 alginate microbeads with or without CXCL12, and postimplantation immunological and histopathological changes were evaluated up to 6 months postimplantation. A similar evaluation of autologous islets in CXCL12-containing alginate microbeads was performed in NHPs (n = 2). Results. CXCL12-containing alginate microbeads were associated with a markedly reduced FBR to microbeads. Host responses to microbead implants were minimal, as assessed by clinical observations, blood counts, and chemistry. Evaluation of encapsulated islets was limited by the development of necrotizing pancreatitis after hemipancreatectomy in 1 NHP. A limited number of functioning islets were detectable at 6 months posttransplantation in the second NHP. In general, empty microbeads or islet-containing beads were found to be evenly distributed through the intraperitoneal cavity and did not accumulate in the Pouch of Douglas. Conclusions. Inclusion of CXCL12 in alginate microbeads minimized localized FBR. The NHP autologous islet implant model had limited utility for excluding inflammatory/immune responses to implanted islets because of the complexity of pancreatic surgery (hemipancreatectomy) before transplantation and the need to micro-encapsulate and transplant encapsulated autologous islets immediately after pancreatectomy and islet isolation.
    Note
    Open access journal
    ISSN
    2373-8731
    PubMed ID
    31165082
    DOI
    10.1097/TXD.0000000000000890
    Version
    Final published version
    Sponsors
    JDRF [2-SRA-2014-290-Q-R]; VIC Innovation Fund
    ae974a485f413a2113503eed53cd6c53
    10.1097/TXD.0000000000000890
    Scopus Count
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