Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model.
Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P<0.001 and P=0.035, respectively). In the following dose titration study, using preimplanted devices, as low as 50 islets cured diabetic mice (100% cure, n=6). We conclude that preimplantation significantly lowers the curative dose of macroencapsulated islets to levels resembling those of free islets transplanted under the renal capsule.
Sörenby
Anne K
AK
Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. anne.sorenby@ki.se
Kumagai-Braesch
Makiko
M
Sharma
Amit
A
Hultenby
Kjell R
KR
Wernerson
Annika M
AM
Tibell
Annika B
AB
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D004703:Endocrine System; D004867:Equipment Design; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006085:Graft Survival; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D019919:Prosthesis Implantation; D013997:Time Factors; D016896:Treatment Outcome
D005947:Glucose