Stable transplantation results of magnetically retracted islets: a novel method

被引:19
作者
Pinkse, GGM
Steenvoorde, E
Hogendoorn, S
Noteborn, M
Terpstra, OT
Bruijn, JA
de Heer, E
机构
[1] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Surg, NL-2300 RC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands
关键词
islets of Langerhans; pancreas; rat; isolation; transplantation; insulin; glucagon;
D O I
10.1007/s00125-003-1268-4
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Aims/hypothesis. Large quantities of pure viable donor islets are necessary for clinical transplantation. At present, low yields and low viability of pancreatic islets after transplantation necessitate the use of multiple donors for a single recipient. In this study an improved method for obtaining large quantities of pure viable islets of Langerhans for transplantation was developed in the rat. Methods. Islets of Langerhans were isolated from Albino Oxford rats. The donor pancreata were perfused in situ with iron oxide, which resulted in entrapment of iron particles in the capillaries of the islets. Subsequently, the islets were isolated by magnetic retraction. Islets obtained with this method were compared with islets obtained by density gradient-isolated islets with respect to yields, purity, and insulin production capacity. Islets isolated with the magnetic retraction method were transplanted under the renal capsule of. streptozotocin-induced diabetic recipients. Blood-glucose levels in the recipients were monitored for 2 months after transplantation. Results. This method yielded more pure and viable islets than the conventional protocol. No contamination of exocrine tissue was observed after isolation. Furthermore, the islets isolated by magnetic retraction stained strongly positive for insulin during the entire observation period in vitro, and produced high amounts of insulin upon a challenge with glucose. The islets that were obtained by this new protocol were suitable for safe and effective transplantation. Conclusions/interpretation. We have shown that both the quantity and quality of islets obtained with this method were sufficient to induce insulin independence in a diabetic recipient using islets from only one donor.
引用
收藏
页码:55 / 61
页数:7
相关论文
共 29 条
[1]
BAELDE JJ, 1994, NEPHROL DIAL TRANSPL, V9, P304
[2]
GLUCAGON IMPROVES INSULIN-SECRETION FROM PIG ISLETS IN-VITRO [J].
BERTUZZI, F ;
BERRA, C ;
SOCCI, C ;
DAVALLI, AM ;
CALORI, G ;
FRESCHI, M ;
PIEMONTI, L ;
DENITTIS, P ;
POZZA, G ;
PONTIROLI, AE .
JOURNAL OF ENDOCRINOLOGY, 1995, 147 (01) :87-93
[3]
Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management [J].
Bretzel, RG ;
Brandhorst, D ;
Brandhorst, H ;
Eckhard, M ;
Ernst, W ;
Freimann, S ;
Rau, W ;
Weimar, B ;
Rauber, K ;
Hering, BJ ;
Brendel, MD .
JOURNAL OF MOLECULAR MEDICINE-JMM, 1999, 77 (01) :140-143
[4]
A comparison of the use of two immunomagnetic microspheres for secondary purification of pancreatic islets [J].
Davies, JE ;
WinotoMorbach, S ;
Ulrichs, K ;
James, RFL ;
Roberts, GSM .
TRANSPLANTATION, 1996, 62 (09) :1301-1306
[5]
OPTIMIZATION OF THE MAGNETIC-FIELD USED FOR IMMUNOMAGNETIC ISLET PURIFICATION [J].
DAVIES, JE ;
JAMES, RFL ;
LONDON, NJM ;
ROBERTSON, GSM .
TRANSPLANTATION, 1995, 59 (05) :767-771
[6]
Why do microencapsulated islet grafts fail in the absence of fibrotic overgrowth? [J].
De Vos, P ;
Van Straaten, JFM ;
Nieuwenhuizen, AG ;
de Groot, M ;
Ploeg, RJ ;
De Haan, PJ ;
Van Schilfgaarde, R .
DIABETES, 1999, 48 (07) :1381-1388
[7]
DISRUPTION OF EPITHELIAL CELL-MATRIX INTERACTIONS INDUCES APOPTOSIS [J].
FRISCH, SM ;
FRANCIS, H .
JOURNAL OF CELL BIOLOGY, 1994, 124 (04) :619-626
[8]
RAPID PURIFICATION OF ISLETS USING MAGNETIC MICROSPHERES COATED WITH ANTI-ACINAR CELL MONOCLONAL-ANTIBODIES [J].
FUJIOKA, T ;
TERASAKI, PI ;
HEINTZ, R ;
MERIDETH, N ;
LANZA, RP ;
ZHENG, TL ;
SOONSHIONG, P .
TRANSPLANTATION, 1990, 49 (02) :404-407
[9]
A METHOD FOR ISOLATION OF MOUSE GLOMERULI FOR QUANTITATION OF IMMUNE DEPOSITS [J].
GAUTHIER, VJ ;
MANNIK, M .
KIDNEY INTERNATIONAL, 1988, 33 (04) :897-899
[10]
IMMUNOLOGICAL CHARACTERISTICS OF PURIFIED PANCREATIC-ISLET GRAFTS [J].
GOTOH, M ;
MAKI, T ;
SATOMI, S ;
PORTER, J ;
MONACO, AP .
TRANSPLANTATION, 1986, 42 (04) :387-390