Microencapsulated dog and rat islet xenografts into streptozotocin-diabetic and NOD mice.
Microencapsulation is an appealing method for islet xenografting. However, graft failure has been related to a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The goal of this study was to characterize this reaction. Poly-l-lysine-alginate microcapsules containing dog or rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and spontaneously diabetic NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody). Both dog and rat islets in microcapsules normalized blood glucose (BG) routinely in both SZN and NOD mice within 24 hours. Empty microcapsules and GK 1.5 treatment did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than 0.01). Graft biopsies showed an intense cellular reaction and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days #70-#95) demonstrated viable islets and no cellular reaction. In prediabetic NODs, encapsulated dog and rat islets elicited a moderate cellular reaction. Empty microcapsules excited no cellular reaction in either diabetic or prediabetic NODs.
Weber
C J
CJ
Luis A. Noboa Laboratory of Surgical Research, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, N.Y.
Zabinsi
S
S
Koschitzky
T
T
Rajotte
R
R
Wicker
L
L
Peterson
L
L
D'Agati
V
V
Reemtsma
K
K
D000818:Animals; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D004285:Dogs; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000276:immunology*
D002214:Capsules; D008567:Membranes, Artificial