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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003627naa a2200373 4500
001oai:prod.swepub.kib.ki.se:147642799
003SwePub
008240701s2021 | |||||||||||000 ||eng|
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1476427992 URI
0247 a https://doi.org/10.1177/096368972110397392 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Yao, Mu Karolinska Institutet4 aut
2451 0a Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation
264 c 2021-09-09
264 1b SAGE Publications,c 2021
520 a During intra-portal pancreatic islet transplantation (PITx), innate immune reactions such as the instant blood mediated inflammatory reaction (IBMIR) cause an immediate loss of islets. The non-hematopoietic erythropoietin analogue cibinetide has previously shown islet-protective effects in mouse PITx. Herein, we aimed to confirm cibinetide’s efficacy on human islets, and to characterize its effect on IBMIR. We cultured human islets with pro-inflammatory cytokines for 18 hours with or without cibinetide. ATP content and caspase 3/7 activity were measured. Dynamic glucose perfusion assay was used to evaluate islet function. To evaluate cibinetides effect on IBMIR, human islets were incubated in heparinized polyvinyl chloride tubing system with ABO compatible blood and rotated for 60 minutes to mimic the portal vein system. Moreover, human islets were transplanted into athymic mice livers via the portal vein with or without perioperative cibinetide treatment. The mice were sacrificed six days following transplantation and the livers were analyzed for human insulin and serum for human C-peptide levels. Histological examination of recipient livers to evaluate islet graft infiltration by CD11b+ cells was performed. Our results show that cibinetide maintained human islet ATP levels and reduced the caspase 3/7 activity during culture with pro-inflammatory cytokines and improved their insulin secreting capacity. In the PVC loop system, administration of cibinetide reduced the IBMIR-induced platelet consumption. In human islet to athymic mice PITx, cibinetide treatment showed an increased amount of human insulin in the livers and higher serum human C-peptide, while histological examination of the livers showed reduced infiltration of pro-inflammatory CD11b+ cells around islets grafts compared to the controls. In summary, Cibinetide protected isolated human islets in a pro-inflammatory milieu and reduced IBMIR related platelet consumption. It improved engraftment of human islets in athymic mice. The study confirms that cibinetide is a promising agent to be used in clinical PITx.
7001 a Domogatskaya, A4 aut
7001 a Agren, IN4 aut
7001 a Watanabe, M4 aut
7001 a Tokodai, K4 aut
7001 a Brines, M4 aut
7001 a Cerami, A4 aut
7001 a Ericzon, BGu Karolinska Institutet4 aut
7001 a Kumagai-Braesch, Mu Karolinska Institutet4 aut
7001 a Lundgren, Tu Karolinska Institutet4 aut
7102 a Karolinska Institutet4 org
7730 t Cell transplantationd : SAGE Publicationsg 30, s. 9636897211039739-q 30<9636897211039739-x 1555-3892x 0963-6897
8564 u https://journals.sagepub.com/doi/pdf/10.1177/09636897211039739
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:147642799
8564 8u https://doi.org/10.1177/09636897211039739

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