Porcine neonatal pancreatic cell clusters (NPCCs): a potential source of tissue for islet transplantation.
This is a short review of porcine neonatal pancreatic cell clusters (NPCCs) which might eventually be useful for beta cell replacement therapy in people with diabetes. The current success with islet allograft transplantation is reviewed and is problematic because only partial success has been obtained and the shortage of human islet tissue means that only a small fraction of people with diabetes would be able to benefit. For these reasons there is considerable interest in xenotransplantation, with pigs being a particularly attractive source. The relative merits of early fetal, late fetal, neonatal and adult porcine tissue are discussed. Neonatal tissue has several attractive features, with their hardiness and potential for growth being especially noteworthy. NPCCs are harvested after digested and dispersed clumps of cells are kept in culture for 7 days. The NPCCs consist mainly of duct cells, protodifferentiated cells and mature endocrine cells. The protodifferentiated cells are either double or triple stained for insulin, cytokeratin 7, glucagon, pancreatic polypeptide, or somatostatin. When transplanted into diabetic nude mice it usually takes weeks before glucose levels are normalized, and during that time differentiation and growth of the graft can be observed. Potential strategies for controlling xenograft rejection are mentioned, with these being immunosuppression, induction of tolerance, immunobarrier devices, and gene transfer approaches.
Weir
G C
GC
Joslin Diabetes Center, Boston, Massachusetts, USA. WeirG@joslab.harvard.edu
Quickel
R R
RR
Yoon
K H
KH
Tatarkiewicz
K
K
Ulrich
T R
TR
Hollister-Lock
J
J
Bonner-Weir
S
S
D000818:Animals; D000831:Animals, Newborn; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D016332:Fetal Tissue Transplantation; D005934:Glucagon / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology* / Q000196:embryology; D016381:Islets of Langerhans Transplantation; D007633:Keratins / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D010191:Pancreatic Polypeptide / Q000032:analysis; D013004:Somatostatin / Q000032:analysis; D013552:Swine; D014183:Transplantation, Heterologous
D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D007633:Keratins; D005934:Glucagon