Quantitative in vivo islet potency assay in normoglycemic nude mice correlates with primary graft function after clinical transplantation.
Reliable assays are critically needed to monitor graft potency in islet transplantation (IT). We tested a quantitative in vivo islet potency assay (QIVIPA) based on human C-peptide (hCP) measurements in normoglycemic nude mice after IT under the kidney capsule. QIVIPA was initially tested by transplanting incremental doses of human islets. hCP levels in mice were correlated with the number of transplanted islet equivalents (r(2) = 0.6, P<0.01). We subsequently evaluated QIVIPA in eight islet preparations transplanted in type 1 diabetic patients. Conversely to standard criteria including islet mass, viability, purity, adenosine triphosphate content, or glucose stimulated insulin secretion, hCP in mice receiving 1% of the final islet product was correlated to primary graft function (hCP increase) after IT (r(2)=0.85, P<0.01). QIVIPA appears as a reliable test to monitor islet graft potency, applicable to validate new methods to produce primary islets or other human insulin secreting cells.
Caiazzo
Robert
R
INSERM U859, Thérapie Cellulaire du Diabète, Faculté de Médecine, Lille, France.
Gmyr
Valery
V
Kremer
Bertrand
B
Hubert
Thomas
T
Soudan
Benoit
B
Lukowiak
Bruno
B
Vandewalle
Brigitte
B
Vantyghem
Marie-Christine
MC
Pattou
Francois
F
Kerr-Conte
Julie
J
D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D005786:Gene Expression Regulation; D006085:Graft Survival; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D011863:Radioimmunoassay; D013997:Time Factors
D002096:C-Peptide; D007328:Insulin