Clinical evolution of diabetic rats after transplant of electrofused pancreatic islet cells and dermic cells

Clinical evolution of diabetic rats after transplant of electrofused pancreatic islet cells and dermic cells
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DOI:
10.1016/j.biopha.2004.11.011
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发表时间:
2005-07-01
影响因子:
7.5
通讯作者:
Román-Ramos, R
Román-Ramos, R
中科院分区:
医学2区
文献类型:
--
作者:
Barrera-Escorcia, E;Muñóz-Torres, A;Román-Ramos, R

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这项工作的目的是研究糖尿病的替代治疗,通过使用杂交细胞的移植获得的胰岛细胞从一个健康的供体与从受体获得的真皮细胞的电融合。杂交细胞保持了胰岛素的产生、调节和对胰岛素分泌的自然控制能力,以及避免排斥反应的组织相容性因素。建立四组,每组四只大鼠:第1组。健康动物(健康对照),第2组。糖尿病未给药动物(糖尿病对照),第3组。移植受体大鼠,提取真皮细胞,与来自健康供体的胰岛细胞混合(移植而不融合),和组4。移植受体大鼠,提取与健康供体胰岛细胞电融合的真皮细胞(融合移植)。对于第4组,将细胞合并,并将其置于具有15 s的0.5 MHz的10 V RMS交流脉冲的介电电泳条件下。用300 V的1 ms直流脉冲进行融合。记录临床体征(体重、利尿、食物和水摄入),并记录血液中的几个生化参数,包括基础胰岛素、尿酸、胆固醇、甘油三酯、谷氨酸-乙酸转氨酶、谷氨酸-丙酮酸转氨酶、尿素、肌酐、胰岛素、糖化血红蛋白。此外,还测量了尿液中的酮体和葡萄糖。所有测定均在30、60和90天进行。第I组动物的参数保持在正常范围内。第2组大鼠在几乎所有测量参数中均出现对应于糖尿病状态的变化,无动物显示自发改善趋势,其中两只大鼠在第66天和第72天死亡。第3组显示出与糖尿病对照组相似的临床特征,没有改善,仅一只大鼠在第33天死亡,而在移植融合的大鼠(第4组)中,观察到一些参数(包括体重、饮水量和体重)的改善。尽管胰岛素浓度低于正常范围,但高于第3组。无大鼠死亡。这些结果表明,通过将来自糖尿病动物的真皮细胞与来自健康供体的岛叶细胞融合移植到受体动物中,可以改善糖尿病特征。(c)2005年,Elsevier SAS。All rights reserved.
This work was designed to study an alternative treatment of diabetes mellitus by using a transplant of hybrid cells obtained by the electrofusion of pancreatic islet cells from a healthy donor with dermic cells obtained from a recipient. The hybrid cells kept the capacity of insulin production, its regulation, and the natural control of glycemia, as well as the factors of histocompatibility to avoid the rejection. Four groups of four rats each were established: Group 1. Healthy animals (healthy control), Group 2. Diabetized non-treated animals (diabetic control), Group 3. Transplant recipient rats with extraction of dermic cells which were mixed with pancreatic insular cells from a healthy donor (transplant without fusion), and Group 4. Transplant recipient rats, with extraction of dermic cells which were electrofused with pancreatic insular cells from a healthy donor (transplant with fusion). For the Group 4, the cells were combined and they were submitted to dielectro-phoresis conditions with an alternating current pulse of 15 s of 10 V RMS of 0.5 MHz. The fusion was made with a direct current pulse of I ms of 300 V. Clinical signs were registered (weight, diuresis, food and water intake), and several biochemical parameters in blood which included basal glycemia, uric acid, cholesterol, triglycerides, glutamate oxalacetate transaminase, glutamate pyruvate transaminase, urea, creatinine, insulin, glycated hemoglobin were registered. Additionally, ketone bodies and glucose were also measured in urine. All determinations were made at 30, 60, and 90 days. Animals of Group I maintained its parameters within the normal ranges. Rats of Group 2 presented alterations corresponding to a diabetic state in almost all the parameters measured, none of the animals showed a tendency to improve spontaneously, two of the rats died at 66 and 72 days. The Group 3 showed a clinical profile similar to the diabetic control group without improvement, only one rat died at day 33, while in the rats transplanted with fusion (Group 4) an improvement was observed on some parameters including body weight, water intake and glycemia. Although insulin concentration was under the normal range, it was higher than in the Group 3. None rat died. These results indicate that it is possible to improve the diabetic profile by the transplant of dermic cells from a diabetic animal fused with insular cells from a healthy donor in the recipient animal. (c) 2005 Elsevier SAS. All rights reserved.