Lelia Wolf-van Buerck1,2, Marion Schuster1,2, Andrea Baehr2,3, Tanja Mayr2,4, Sonja Guethoff2,4, Jan Abicht2,5, Bruno Reichart2, Yun-Chung Nam-Apostolopoulos6, Nikolai Klymiuk2,3, Eckhard Wolf2,3, Jochen Seissler1,2. 1. Medizinische Klinik und Poliklinik IV-Campus Innenstadt, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität, München, Germany. 2. Transregio Collaborative Research Center 127, Ludwig-Maximilians-Universität, München, Germany. 3. Chair for Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität, München, Germany. 4. Department of Cardiac Surgery, Ludwig-Maximilians-Universität, München, Germany. 5. Department of Anesthesiology, Ludwig-Maximilians-Universität, München, Germany. 6. Institute of Pathology, Ludwig-Maximilians-Universität, München, Germany.
Abstract
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 (NPICCs) 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 IL2rγ(-/-) (NSG) mice. Survival, vascularization, maturation, and functional activity were analyzed by intraperitoneal glucose tolerance testing and immunohistochemical analyses. RESULTS: Intramuscular transplantation of NPICCs 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 NPICCs 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.
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 (NPICCs) 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 IL2rγ(-/-) (NSG) mice. Survival, vascularization, maturation, and functional activity were analyzed by intraperitoneal glucose tolerance testing and immunohistochemical analyses. RESULTS: Intramuscular transplantation of NPICCs 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 NPICCs 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.
Authors: Elisabeth Kemter; Christian M Cohrs; Matthias Schäfer; Marion Schuster; Klaus Steinmeyer; Lelia Wolf-van Buerck; Andrea Wolf; Annegret Wuensch; Mayuko Kurome; Barbara Kessler; Valeri Zakhartchenko; Matthias Loehn; Yuri Ivashchenko; Jochen Seissler; Anke M Schulte; Stephan Speier; Eckhard Wolf Journal: Diabetologia Date: 2017-03-18 Impact factor: 10.122
Authors: A Shishido; A Caicedo; R Rodriguez-Diaz; A Pileggi; P-O Berggren; M H Abdulreda Journal: CellR4 Repair Replace Regen Reprogram Date: 2016-07-26
Authors: Midhat H Abdulreda; Dora M Berman; Alexander Shishido; Christopher Martin; Maged Hossameldin; Ashley Tschiggfrie; Luis F Hernandez; Ana Hernandez; Camillo Ricordi; Jean-Marie Parel; Ewa Jankowska-Gan; William J Burlingham; Esdras A Arrieta-Quintero; Victor L Perez; Norma S Kenyon; Per-Olof Berggren Journal: Diabetologia Date: 2019-01-31 Impact factor: 10.122
Authors: L Wolf-van Buerck; M Schuster; F S Oduncu; A Baehr; T Mayr; S Guethoff; J Abicht; B Reichart; N Klymiuk; E Wolf; J Seissler Journal: Sci Rep Date: 2017-06-15 Impact factor: 4.379