Growing Trans-Species Islets in Tumor Extract-Remodeled Testicles
Growing Trans-Species Islets in Tumor Extract-Remodeled Testicles
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在肿瘤提取物重塑睾丸中生长跨物种胰岛
DOI：
10.1002/advs.201801694
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发表时间：
2019
期刊：
影响因子：
15.1
通讯作者：
Dong Lei
中科院分区：
文献类型：
--
作者：
Wang Zhenzhen;Rui Xiaying;Qiu Junni;Yan Yiqing;Gan Jingjing;Liu Shang;Wang Lintao;Zhang Junfeng;Wang Chunming;Dong Lei
尽管胰岛移植有望治疗I型糖尿病，但其应用受到移植排斥反应的严重阻碍。本研究证明了一种方法可以支持来自大鼠的跨物种胰岛β细胞在小鼠宿主体内生长和功能，同时克服移植排斥反应。这种方法建立在通过局部注射肿瘤匀浆重建小鼠睾丸的基础上，在睾丸中建立免疫抑制和促进再生的生态位。这种重塑被证明是必要和有效的，将睾丸塑造成一个独特的位置，以容纳异种移植细胞。来自胰岛素瘤（癌细胞）和胰岛（正常组织）的大鼠胰腺β细胞在重建的小鼠睾丸中存活、生长并形成理想的形态。值得注意的是，当宿主体内诱导高血糖时，这些异种移植物分泌胰岛素来调节小鼠的血糖水平长达72天。此外，在整个研究中没有观察到移植排斥反应、急性炎症或安全风险。总之，这表明异种胰岛素瘤细胞在小鼠睾丸中的生长可能作为胰岛移植的一种替代方法。
Although pancreatic islet transplantation holds promise for the treatment of type I diabetes, its application has been significantly hampered by transplant rejection. Here, an approach is demonstrated to support trans‐species islet beta cells from a rat to grow and function in the body of a mouse host while overcoming graft rejection. This approach, which builds on remodeling of the mouse testicle by local injection of a tumor homogenate, establishes an immunosuppressive and proregenerative niche in the testicle. This remodeling proves necessary and effective in shaping the testicle into a unique site to accommodate xenograft cells. Rat pancreatic beta cells—from both the insulinoma (cancer cells) and pancreatic islet (normal tissue)—survive, grow, and form a desirable morphology in the remodeled mouse testicle. Notably, when hyperglycemia is induced in the host body, these xenografts secrete insulin to regulate the blood glucose level in mice for as long as 72 days. Furthermore, no graft rejection, acute inflammation, or safety risks are observed throughout the study. In summary, it is demonstrated that the growth of xenogeneic insulinoma cells in a mouse testicle might serve as an alternative approach for islet transplantation.