Evaluation of alternative sites for islet transplantation in the minipig: Interest and limits of the gastric submucosa

Evaluation of alternative sites for islet transplantation in the minipig: Interest and limits of the gastric submucosa
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DOI:
10.1016/j.transproceed.2007.08.015
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发表时间:
2007-10-01
影响因子:
0.9
通讯作者:
Pattou, F.
Pattou, F.
中科院分区:
医学4区
文献类型:
--
作者:
Caiazzo, R.;Gmyr, V.;Pattou, F.

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自从无糖皮质激素免疫抑制方案的引入,胰岛移植为胰腺移植提供了一种侵入性较小的替代方案。然而,与门静脉内胰岛注射相关的并发症和肝内胰岛功能的进行性下降鼓励了对替代部位的探索。在此,我们评估了在小型猪中,与肾包膜(KC;组2,n = 5)相比,胃粘膜下层(GS;组1,n = 5)用于胰岛移植的用途。随后,我们试图通过添加富含生长因子的细胞外基质(Matrigel)来改善粘膜下移植物的血管化(第3组,n = 5)。移植后一个月,我们在体内和体外评估移植的胰岛功能。我们的研究显示移植在GS中的胰岛功能优于KC(P <0.05)。尽管有生长因子,但基质胶没有提供更合适的环境来进一步改善植入(组3,P <0.05)。因此,即使肝脏仍然是金标准,GS代表了一个潜在的胰岛移植部位,证实了在体外和啮齿动物中获得的数据。通过内窥镜检查,该网站提供了方便,可能构成一个有趣的替代大型哺乳动物的实验研究,并最终为临床应用。
Since the introduction of glucocorticoid-free immunosuppressive regimens, islet transplantation offers a less invasive alternative to pancreas transplantation. However, complications associated with intraportal islet injection and the progressive functional decline of intrahepatic islets encourage the exploration of alternative sites. Herein we evaluated, in the minipig, the use of the gastric submucosa (GS; group 1, n = 5) for islet transplantation compared with the kidney capsule (KC; group 2, n = 5). Subsequently we attempted to improve the vascularization of the submucosal graft (group 3, n = 5) by the addition of an extracellular matrix rich in growth factors (Matrigel). One month after grafting, we evaluated transplanted islet function in vivo and in vitro. Our study showed better function of islets engrafted in the GS than in the KC (P < .05). Despite the growth factors, Matrigel did not offer a more suitable environment to further improve engraftment (group 3, P < .05). Thus, even if the liver remains the gold standard, the GS represents a potential islet engraftment site, confirming the data obtained in vitro and in the rodent. Offering easy access by endoscopy, this site could constitute an interesting alternative for experimental studies in large mammals and, eventually, for clinical application.