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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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Author
Sremac, MarinkoLei, 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
Affiliation
Univ Arizona, Dept Surg, Inst Cellular TransplantatIssue Date
2019-04-15
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LIPPINCOTT WILLIAMS & WILKINSCitation
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 DIRECTRights
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 (CC BY-NC-ND).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 journalISSN
2373-8731PubMed ID
31165082Version
Final published versionSponsors
JDRF [2-SRA-2014-290-Q-R]; VIC Innovation Fundae974a485f413a2113503eed53cd6c53
10.1097/TXD.0000000000000890
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Except where otherwise noted, this item's license is described as 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 (CC BY-NC-ND).
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