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Engraftment and reversal of diabetes after intramuscular transplantation of neonatal porcine islet‐like clusters
Author(s) -
Wolfvan Buerck Lelia,
Schuster Marion,
Baehr Andrea,
Mayr Tanja,
Guethoff Sonja,
Abicht Jan,
Reichart Bruno,
NamApostolopoulos YunChung,
Klymiuk Nikolai,
Wolf Eckhard,
Seissler Jochen
Publication year - 2015
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12201
Subject(s) - xenotransplantation , transplantation , islet , medicine , diabetes mellitus , glucose homeostasis , intramuscular injection , endocrinology , insulin resistance
Background Intraportal infusion is currently the method of choice for clinical islet cell transplantation but suffers from poor efficacy. As the liver may not represent an optimal transplantation site for Langerhans islets, we examined the potential of neonatal porcine islet‐like clusters ( NPICC s) to engraft in skeletal muscle as an alternative transplantation site. Methods Neonatal porcine islet‐like clusters were isolated from 2‐ to 5‐day‐old piglets and either transplanted under the kidney capsule (s.k.) or injected into the lower hindlimb muscle (i.m.) of streptozotocin‐diabetic NOD ‐ SCID IL 2rγ −/− ( NSG ) mice. Survival, vascularization, maturation, and functional activity were analyzed by intraperitoneal glucose tolerance testing and immunohistochemical analyses. Results Intramuscular transplantation of NPICC s resulted in development of normoglycemia and restored glucose homeostasis. Time to reversal of diabetes and glucose tolerance ( AUC glucose and AUC insulin) did not significantly differ as compared to s.k. transplantation. Intramuscular grafts exhibited rapid neovascularization and graft composition with cytokeratin‐positive ductal cells and beta cells at post‐transplant weeks 2 and 8 and after establishment of normoglycemia was comparable in both groups. Conclusions Intramuscular injection represents a minimally invasive but efficient alternative for transplantation of NPICC s and, thus, offers an attractive alternative site for xenotransplantation approaches. These findings may have important implications for improving the outcome and the monitoring of pig islet xenotransplantation.