Prolonged glucose normalization of streptozotocin-induced diabetic mice by transplantation of rat islets coencapsulated with crosslinked hemoglobin.
BACKGROUND
Facilitated oxygen transport by crosslinked hemoglobin (Hb-C) in islet microcapsules may promote transplanted graft function by improving islet functionality and viability.


METHODS
This study investigated the in vivo efficacy of Hb-C as an oxygen carrier on the functionality and viability of microencapsulated rat islets. Hb-C by poly(ethylene glycol) was introduced into rat islet microcapsules (alginate-poly[L-lysine]-alginate microcapsule), and 500 suboptimal encapsulated islets were xenotransplanted into each streptozotocin-induced diabetic BALB/c mouse. The graft efficacy over time was evaluated by measuring nonfasting blood glucose level, body weight, and glucose tolerance.


RESULTS
Mice that received Hb-C-containing microcapsules maintained normoglycemia for at least 8 weeks with normal glucose clearance, determined by intraperitoneal glucose tolerance test. However, the mice that received the conventional control islet microcapsule (without Hb-C) transplant showed graft failure in 4 weeks, exhibited by hyperglycemia, weight loss, and deteriorated glucose tolerance. Severe central necrosis of retrieved islets was observed for the control islet capsule graft after 8 weeks.


CONCLUSIONS
The present study revealed that the incorporation of Hb-C in islet microcapsules promotes graft function for a longer period of time than the conventional islet capsules. Therefore, Hb-C coencapsulation is a potential approach for prolonging graft function of islet microcapsules and reducing the number of islets required for normoglycemia.
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, USA.
Su Young
SY
Chae
Yong Yeon
YY
Kim
Sung Wan
SW
Kim
You Han
YH
Bae
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D002214:Capsules; D003432:Cross-Linking Reagents; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005951:Glucose Tolerance Test; D006454:Hemoglobins; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D001786:Blood Glucose; D002214:Capsules; D003432:Cross-Linking Reagents; D006454:Hemoglobins