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Engraftment of cells from porcine islets of Langerhans following transplantation of pig pancreatic primordia in non-immunosuppressed diabetic rhesus macaques.
- Source :
-
Organogenesis [Organogenesis] 2011 Jul-Sep; Vol. 7 (3), pp. 154-62. Date of Electronic Publication: 2011 Jul 01. - Publication Year :
- 2011
-
Abstract
- Transplantation therapy for human diabetes is limited by the toxicity of immunosuppressive drugs. If toxicity can be minimized, there will still be a shortage of human donor organs. Xenotransplantation of porcine islets is a strategy to overcome supply problems. Xenotransplantation in mesentery of pig pancreatic primordia obtained very early during organogenesis [embryonic day 28 (E28)] is a way to obviate the need for immunosuppression in rats or rhesus macaques and to enable engraftment of a cell component originating from porcine islets implanted beneath the renal capsule of rats. Here, we show engraftment in the kidney of insulin and porcine proinsulin mRNA-expressing cells following implantation of porcine islets beneath the renal capsule of diabetic rhesus macaques transplanted previously with E28 pig pancreatic primordia in mesentery. Donor cell engraftment is confirmed using fluorescent in situ hybridization (FISH) for the porcine X chromosome and is supported by glucose-stimulated insulin release in vitro. Cells from islets do not engraft in the kidney without prior transplantation of E28 pig pancreatic primordia in mesentery. This is the first report of engraftment following transplantation of porcine islets in non-immunosuppressed, immune-competent non-human primates. The data are consistent with tolerance to a cell component of porcine islets induced by previous transplantation of E28 pig pancreatic primordia.
- Subjects :
- Animals
Diabetes Mellitus, Experimental immunology
Diabetes Mellitus, Experimental therapy
Embryo, Mammalian
Graft Survival
Immunosuppression Therapy
Insulin genetics
Insulin metabolism
Insulin Secretion
Islets of Langerhans pathology
Kidney pathology
Macaca mulatta
Mesentery surgery
Pancreas Transplantation
Proinsulin genetics
Proinsulin metabolism
RNA, Messenger metabolism
Swine
Transplantation, Heterologous immunology
Diabetes Mellitus, Experimental pathology
Islets of Langerhans Transplantation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1555-8592
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Organogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 21654197
- Full Text :
- https://doi.org/10.4161/org.7.3.16522