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

Improved survival of microencapsulated islets during in vitro culture and enhanced metabolic function following transplantation
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DOI:
10.1007/s00125-004-1531-3
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发表时间:
2004-10-01
期刊:
影响因子:
8.2
通讯作者:
Rajotte, RV
Rajotte, RV
中科院分区:
医学1区
文献类型:
--
作者:
Korbutt, GS;Mallett, AG;Rajotte, RV

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目标/假设。本研究的目的是确定在长期的组织培养过程中,简单的藻酸盐胶囊是否能够延长胰岛的存活和功能。我们还想观察这些包裹的胰岛恢复糖尿病受者的血糖反应性的能力,以及这样做所需的胰岛数量。在组织培养1周、2周、3周后,比较包膜与非包膜胰岛的修复和代谢功能。这些培养制剂也被移植到糖尿病裸鼠体内,并比较了它们逆转糖尿病的能力。此外,短期培养的囊化和非囊化胰岛被不同数量的移植,以确定使血糖正常化和延长受体存活所需的最小剂量。组织培养1周、2周和3周的胰岛复原率明显高于包裹胰岛组。当这些胰岛在1、2和3周恢复并移植到糖尿病裸鼠体内时,所有包膜组的100d存活率均为100%,而未包膜的胰岛分别为66%、33%和33%。此外,当胰岛被包裹时,需要大量短期培养的胰岛来使血糖正常化。囊化胰岛受者的存活时间也显著长于非囊化制剂的受者。这项研究表明,用纯化的海藻酸盐包裹胰岛可以改善胰岛在体外和体内的存活和功能。
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.