Improved survival of microencapsulated islets during in vitro culture and enhanced metabolic function following transplantation

被引:54
作者
Korbutt, GS
Mallett, AG
Ao, Z
Flashner, M
Rajotte, RV
机构
[1] Univ Alberta, Surg Med Res Inst, Edmonton, AB T6G 2N8, Canada
[2] Univ Alberta, Dept Surg, Edmonton, AB, Canada
[3] Univ British Columbia, UBG VGH Clin Islet Lab, Vancouver, BC V5Z 1M9, Canada
[4] EGB Advisors LLC, San Francisco, CA USA
[5] Univ Alberta, Dept Med, Edmonton, AB, Canada
基金
加拿大健康研究院;
关键词
alginate; capsules; diabetes; dogs; insulin; islet transplantation; mice; microencapsulation; tissue culture; transplantation;
D O I
10.1007/s00125-004-1531-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. The aim of this study was to determine whether a simple alginate capsule can prolong islet survival and function during long-term tissue culture. We also wanted to observe the ability of these encapsulated islets to restore glucose responsiveness to diabetic recipients, along with the quantity of islets required to do so. Methods. We compared the recovery and metabolic function of encapsulated canine islets with that of non-encapsulated canine islets following 1, 2 or 3 weeks of tissue culture. These culture preparations were also transplanted into diabetic nude mice and compared for their ability to reverse diabetes. Furthermore, short-term cultured encapsulated and non-encapsulated islets were transplanted in varying numbers to determine the minimum dose required to normalise blood glucose and prolong recipient survival. Results. Islet recovery following 1, 2 and 3 weeks of tissue culture was significantly higher when islets were encapsulated. When these islets were recovered at 1, 2 and 3 weeks and transplanted into diabetic nude mice, survival at 100 days was 100% for all encapsulated groups, versus 66%, 33% and 33% respectively for the non-encapsulated islets. Additionally, substantially fewer short-term cultured islets were required to normalise blood glucose when the islets were encapsulated. Recipients of encapsulated islets also had significantly longer survival times than recipients of non-encapsulated preparations. Conclusions/interpretation. This study demonstrates that encapsulation of islets with purified alginate improves islet survival and function in vitro and in vivo.
引用
收藏
页码:1810 / 1818
页数:9
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