Functional and Immunohistochemical Evaluation of Porcine Neonatal Islet-Like Cell Clusters
Functional and Immunohistochemical Evaluation of Porcine Neonatal Islet-Like Cell Clusters
复制标题
猪新生胰岛样细胞簇的功能和免疫组织化学评价
作者：
T. Nielsen;K. Yderstraede;H. Schrøder;J. Holst;K. Brusgaard;H. Beck
猪新生胰岛样细胞团（NICCs）可能是一个有吸引力的来源，产生胰岛素的组织异种移植在I型糖尿病患者。我们研究了胰岛移植物在体外长期培养和移植到无胸腺裸鼠体内后的功能和免疫组化结果。我们从每个胰腺平均获得29，000个NICC。在灌流系统中，NICCs对单独葡萄糖刺激反应不佳，但10 mmol/L精氨酸引起胰岛素分泌增加4倍，16.7 mmol/L葡萄糖+ 10 mmol/L精氨酸引起胰岛素分泌增加7倍，表明对葡萄糖具有一定的敏感性。激素含量，以及含激素的细胞的数量增加的第一个14天的文化。当NICCs被染色用于激素、增殖（Ki 67）和导管细胞（CK 7）时，一些胰岛素和胰高血糖素阳性细胞共染色用于增殖。然而，在胰岛素和胰高血糖素阳性细胞之间或在激素和CK 7阳性细胞之间未观察到共染色。在糖尿病裸鼠的肾包膜下移植2000个NICC后，BG水平在平均13周内正常化。口服和IP葡萄糖耐量试验显示，与正常对照组相比，葡萄糖负荷的清除正常或甚至更快。移植物的免疫组织化学检查显示主要是胰岛素阳性细胞。总之，在体外，NICC对包括葡萄糖和精氨酸的激发有反应。在体外以及体内存在NICC的β-细胞团扩增的潜力，其中NICC最终可使糖尿病小鼠的血糖正常化。
Porcine neonatal islet-like cell clusters (NICCs) may be an attractive source of insulin-producing tissue for xenotransplantation in type I diabetic patients. We examined the functional and immunohistochemical outcome of the islet grafts in vitro during long-term culture and in vivo after transplantation to athymic nude mice. On average we obtained 29,000 NICCs from each pancreas. In a perifusion system, NICCs responded poorly to a glucose challenge alone, but 10 mmol/L arginine elicited a fourfold increase in insulin secretion and 16.7 mmol/L glucose + 10 mmol/L arginine caused a sevenfold increase in insulin secretion, indicating some sensitivity towards glucose. Hormone content as well as the number of hormone-containing cells increased for the first 14 days of culture. When NICCs were stained for hormones, proliferation (Ki67), and duct cells (CK7), some insulin- and glucagon-positive cells co-stained for proliferation. However no co-staining was observed between insulin- and glucagon-positive cells or between hormone- and CK7-positive cells. Following transplantation of 2000 NICCs under the renal capsule of diabetic nude mice, BG levels were normalized within an average of 13 weeks. Oral and IP glucose tolerance tests revealed a normal or even faster clearance of a glucose load compared with normal controls. Immunohistochemical examination of the grafts revealed primarily insulin-positive cells. In summary, in vitro, NICCs responded to a challenge including glucose and arginine. There was a potential for expansion of the β-cell mass of NICCs in vitro as well as in vivo where NICCs eventually may normalize blood glucose of diabetic mice.
登录
查看更多内容
猪新生胰腺细胞簇（NPCC）：胰岛移植的潜在组织来源。
影响因子：
1.1
作者：
Weir,GC;Quickel,RR;Yoon,KH;Tatarkiewicz,K;Ulrich,TR;Hollister-Lock,J;Bonner-Weir,S
通讯作者：
Bonner-Weir,S
影响因子：
7.7
作者：
Jensen, J;Heller, RS;Serup, P
通讯作者：
Serup, P
DOI：
--
发表时间：
1992
期刊：
The Yale journal of biology and medicine
影响因子：
--
作者：
Vinik,A;Pittenger,G;Rafaeloff,R;Rosenberg,L
通讯作者：
Rosenberg,L
影响因子：
15.9
作者：
OTONKOSKI, T;BEATTIE, GM;HAYEK, A
通讯作者：
HAYEK, A