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顺磁微颗粒在共培养或植入后的宿主免疫反应中不会引起胰岛细胞毒性。

Paramagnetic microparticles do not elicit islet cytotoxicity with co-culture or host immune reactivity after implantation.

机构信息

Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN 55401, USA.

出版信息

Xenotransplantation. 2011 Jul-Aug;18(4):239-44. doi: 10.1111/j.1399-3089.2011.00648.x.

DOI:10.1111/j.1399-3089.2011.00648.x
PMID:21848541
Abstract

BACKGROUND

Paramagnetic microparticles (MPs) may be useful in pancreatic islet purification, in particular purification of porcine islets as a potential xenotransplantation product. We assessed whether MPs affect islet function or induce an adverse effect following implantation.

METHODS

Porcine islets were co-cultured with 0, 500, and 1500 MPs per islet equivalent (IE) for 1 day and with 0 and 1500 MPs/IE for 7 days. Fractional viability was assessed using oxygen consumption rate normalized to DNA content (OCR/DNA) and after 7-day co-culture by perifusion glucose-stimulated insulin secretion (GSIS) and by transplantation under the renal capsule of diabetic nude mice. To assess an inflammatory response or immune reaction, MPs (∼10(7)) were implanted under the renal capsule of C57BL/6 mice.

RESULTS

No statistically significant differences were measured in OCR/DNA (mean ± SE) following 1-day co-culture with 0, 500, or 1500 MPs/IE (243.3 ± 4.5, 211.3 ± 8.1, or 230.6 ± 11.3 nmol/min·mgDNA, respectively) or following 7-day co-culture with 0 or 1500 MPs/IE (248.5 ± 1.4 or 252.9 ± 4.7 nmol/min·mgDNA, respectively). GSIS was not affected by the presence of MPs; first- and second-phase insulin area-under-the-curve (mean ± SE) reflected no statistically significant differences after 7-day co-culture between 0 and 1500 MPs/IE (8.36 ± 0.29 and 8.45 ± 0.70 pg/ml·min·ngDNA for first-phase; 69.73 ± 2.18 and 65.70 ± 4.34 pg/ml·min·ngDNA for second-phase, respectively). Islets co-cultured with MPs normalized hyperglycemia in diabetic nude mice, suggesting no adverse effects on in vivo islet function. Implantation of MPs did not elicit tissue injury, inflammatory change or immune reactivity.

CONCLUSION

MPs do not adversely affect islet viability or function during co-culture, and MPs are not immune reactive following implantation.

摘要

背景

顺磁微球(MPs)在胰岛纯化中可能有用,特别是作为潜在异种移植产品的猪胰岛的纯化。我们评估了 MPs 是否会影响胰岛功能或在植入后产生不良反应。

方法

将猪胰岛与 0、500 和 1500 个 MPs/IE 进行 1 天共培养,与 0 和 1500 MPs/IE 进行 7 天共培养。通过氧消耗率与 DNA 含量的比值(OCR/DNA)评估部分活力,并在 7 天共培养后通过胰岛移植下糖尿病裸鼠肾囊下的葡萄糖刺激胰岛素分泌(GSIS)和 Perifusion 进行评估。为了评估炎症反应或免疫反应,将大约 10(7) MPs 植入 C57BL/6 小鼠的肾囊下。

结果

在与 0、500 或 1500 MPs/IE 进行 1 天共培养后,OCR/DNA(平均值±SE)无统计学差异(分别为 243.3±4.5、211.3±8.1 或 230.6±11.3 nmol/min·mgDNA),在与 0 或 1500 MPs/IE 进行 7 天共培养后,OCR/DNA 也无统计学差异(分别为 248.5±1.4 或 252.9±4.7 nmol/min·mgDNA)。 MPs 不影响 GSIS;经过 7 天共培养后,第一和第二相胰岛素曲线下面积(mean±SE)在 0 与 1500 MPs/IE 之间无统计学差异(第一相分别为 8.36±0.29 和 8.45±0.70 pg/ml·min·ngDNA;第二相分别为 69.73±2.18 和 65.70±4.34 pg/ml·min·ngDNA)。与 MPs 共培养的胰岛使糖尿病裸鼠的高血糖正常化,表明对体内胰岛功能无不良影响。 MPs 的植入不会引起组织损伤、炎症变化或免疫反应。

结论

MPs 在共培养过程中不会对胰岛的活力或功能产生不利影响,植入后也不会引起免疫反应。

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