Prolonged survival of microencapsulated neonatal porcine islet xenografts in immune-competent mice without antirejection therapy.
Several studies have demonstrated that in vitro culture of islets prolonged islet graft survival in immune-competent mice without administration of antirejection drugs. However, we recently showed that in vitro cultured microencapsulated neonatal porcine islets (NPI) were rejected in immune-competent mice not receiving antirejection therapy. The aim of this study was to determine whether culture of microencapsulated NPI in vivo could promote long-term survival of microencapsulated NPI in immune-competent mice without administration of antirejection drugs. Microencapsulated NPI that were cultured in vitro for 7 and 50 days or transplanted initially in immune-deficient C.B.-17 SCID-BEIGE mice for 100 days (in vivo cultured) were characterized and transplanted into streptozotocin-induced diabetic immune-competent BALB/c mice. Day 50 in vitro cultured and day 100 in vivo cultured microencapsulated NPI showed significantly higher insulin and DNA content, indicating maturation of NPI compared to day 7 in vitro cultured microencapsulated NPI. Interestingly, in vivo cultured microencapsulated NPI expressed lower levels of porcine antigens compared to day 7 and day 50 in vitro cultured microencapsulated NPI. Transplantation of day 7 in vitro cultured microencapsulated NPI did not reverse diabetes in immune-competent BALB/c mouse recipients. In contrast, transplantation of day 50 in vitro cultured and in vivo cultured microencapsulated NPI into diabetic immune-competent BALB/c mice resulted in the immediate reversal of hyperglycemia within 2 days posttransplantation. However, all recipients of day 50 in vitro cultured microencapsulated NPI eventually rejected their grafts by day 15 posttransplantation, while 6 of 10 BALB/c mouse recipients of in vivo cultured microencapsulated NPI maintained normoglycemia for 100 days posttransplantation. These results show that in vivo culture of NPI in immune-deficient mice results in the modulation of NPI, which allows for their long-term survival in immune-competent mice without antirejection therapy.
Kobayashi
Tsunehiro
T
Surgical-Medical Research Institute, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Arefanian
Hossein
H
Harb
George
G
Tredget
Eric B
EB
Rajotte
Ray V
RV
Korbutt
Gregory S
GS
Rayat
Gina R
GR
D000818:Animals; D000831:Animals, Newborn; D004339:Drug Compounding / Q000379:methods; D005260:Female; D006085:Graft Survival / Q000276:immunology; D007121:Immunocompetence / Q000235:genetics / Q000502:physiology*; D007165:Immunosuppression Therapy; D047908:Intracellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000276:immunology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics; D013552:Swine; D013997:Time Factors; D033921:Vesicular Transport Proteins
D047908:Intracellular Signaling Peptides and Proteins; C491133:Lyst protein, mouse; D011506:Proteins; D033921:Vesicular Transport Proteins