Caiazzo R, Gmyr V, Hubert T, Delalleau N, Lamberts R, Moerman E, Kerr-Conte J, Pattou F
INSERM UNIT-M 859, Diabetes Cell Therapy, Faculty of Medicine, Lille 2 University, 1 Place de Verdun, 59045 Lille, France.
Transplant Proc. 2007 Oct;39(8):2620-3. doi: 10.1016/j.transproceed.2007.08.015.
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.
自从引入无糖皮质激素的免疫抑制方案以来,胰岛移植为胰腺移植提供了一种侵入性较小的替代方法。然而,与门静脉内胰岛注射相关的并发症以及肝内胰岛功能的逐渐衰退促使人们探索其他替代部位。在此,我们在小型猪中评估了胃黏膜下层(GS;第1组,n = 5)用于胰岛移植的情况,并与肾被膜(KC;第2组,n = 5)进行了比较。随后,我们试图通过添加富含生长因子的细胞外基质(基质胶)来改善黏膜下移植体的血管化(第3组,n = 5)。移植后一个月,我们在体内和体外评估了移植胰岛的功能。我们的研究表明,植入GS的胰岛功能优于植入KC的胰岛(P < 0.05)。尽管有生长因子,基质胶并未提供更合适的环境来进一步改善植入情况(第3组,P < 0.05)。因此,即使肝脏仍然是金标准,GS也是一个潜在的胰岛植入部位,这证实了在体外和啮齿动物中获得的数据。通过内镜检查易于进入该部位,这可能成为大型哺乳动物实验研究以及最终临床应用的一个有趣替代方法。