Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI.
Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI.
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DOI：
10.1097/tp.0000000000000682
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发表时间：
2015-08
期刊：
影响因子：
6.2
通讯作者：
Moore A
中科院分区：
文献类型：
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作者：
Wang P;Schuetz C;Vallabhajosyula P;Medarova Z;Tena A;Wei L;Yamada K;Deng S;Markmann JF;Sachs DH;Moore A
关于胰岛移植物寿命的信息可以为治疗方案提供有价值的信息。在我们以前的研究中，我们发现分离的自体胰岛可以用氧化铁纳米颗粒标记，并在移植后使用磁共振成像进行监测。在这里，我们报告在体内监测的二次损伤，发生在后期阶段，由于同种异体免疫排斥反应。在原理验证研究中，将氧化铁标记的自体胰岛移植到非人灵长类动物的肾囊下。为了证明急性移植物丢失，动物注射链脲佐菌素（STZ）。通过体内MRI进行移植物监测。接下来，将氧化铁标记的同种异体胰岛移植到肝脏中，并在取消免疫抑制后通过MRI进行监测。在自体模型中，通过MRI评估，我们观察到STZ激发后移植物体积明显下降。在同种异体胰岛移植模型中，手术后出现最初的胰岛损失，随后移植物体积相对稳定。免疫抑制停止后，移植物体积明显下降，并在研究过程中逐渐持续。重要的是，MR上观察到的移植物体积损失先于血糖升高。本研究表明，体内MRI能够在血糖发生任何变化之前显示移植物体积损失，这些变化可以通过标准方法测量。我们相信，这些结果可以为临床医生提供手段，以遵循胰岛的命运非侵入性和纵向使用临床相关的扫描仪。
Information regarding the longevity of transplanted pancreatic islet grafts could provide valuable information for treatment options. In our previous studies we showed that isolated autologous pancreatic islets could be labeled with iron oxide nanoparticles and monitored following transplantation using magnetic resonance imaging. Here, we report on in vivo monitoring of a secondary damage that occurs at the later stages due to allogeneic immune rejection. In the proof-o-principle studies, iron oxide-labeled autologous pancreatic islets were transplanted under the renal capsules of non-human primates. To demonstrate acute graft loss, the animals were injected with streptozotocin (STZ). Graft monitoring was performed by in vivo MRI. Next, iron oxide-labeled allogeneic islets were transplanted into the liver and monitored by MRI after withdrawal of immunosuppression. In autologous model we observed a pronounced drop in graft volume after STZ challenge as assessed by MRI. In allogeneic model of islet transplantation, there was an initial islet loss after the procedure followed by relative stabilization of the graft volume. After immunosuppression was discontinued there was a noticeable drop in graft volume that gradually continued during the course of the study. Importantly, the loss of graft volume observed on MR preceded the raise in blood glucose. This study demonstrated that in vivo MRI was able to reveal graft volume loss prior to any changes in blood glucose that can be measured by standard methods. We believe that these results could provide means for clinicians to follow islet fate non-invasively and longitudinally using clinically relevant scanners.