后腹腔结肠后间隙作为包裹异种胰岛移植部位的优势。
Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets.
机构信息
Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
出版信息
Xenotransplantation. 2023 Jan;30(1):e12787. doi: 10.1111/xen.12787. Epub 2022 Dec 1.
OBJECTIVE
Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application. To find a new strategy, we tested a new polymer combination for islet encapsulation and transplantation. Meanwhile, we explored a new site for xenogeneic islet transplantation in mice.
METHOD
We synthesized a hydrogel combining alginate plus poly-ethylene-imine (Alg/PEI) for the encapsulation of rat, neonatal porcine, and human islets. Transplantation was performed into the retroperitoneal retro-colic space of diabetic mice. Control mice received free islets under the kidney capsule or encapsulated islets into the peritoneum. The biochemical indexes were measured, and the transplanted islets were harvested for immunohistochemical staining of insulin and glucagon.
RESULTS
Mice receiving encapsulated rat, porcine and human islets transplanted into the retroperitoneal space maintained normoglycemia for a median of 275, 145.5, and 146 days, respectively. In contrast, encapsulated xenogeneic islets transplanted into the peritoneum, maintained function for a median of 61, 95.5, and 82 days, respectively. Meanwhile, xenogeneic islets transplanted free into the kidney capsule lost their function within 3 days after transplantation. Immunohistochemical staining of encapsulated rat, porcine and human islets, retrieved from the retroperitoneal space, allowed to distinguish morphological normal insulin expressing β- and glucagon expressing α-cells at 70, 60, and 100 days post-transplant, respectively.
CONCLUSION
Transplantation of Alg/PEI encapsulated xenogeneic islets into the retroperitoneal space provides a valuable new implantation strategy for the treatment of type 1 diabetes.
目的
胰岛同种异体移植已证明使用肝门静脉作为标准输注方法可改善临床结果。然而，目前的植入部位并不理想，因为存在短期血栓形成和长期免疫破坏。同时，人类器官供体的短缺进一步限制了其应用。为了寻找新的策略，我们测试了一种用于胰岛包封和移植的新聚合物组合。同时，我们在小鼠中探索了异种胰岛移植的新部位。
方法
我们合成了一种结合海藻酸钠和聚亚乙基亚胺（Alg/PEI）的水凝胶，用于包封大鼠、新生猪和人胰岛。将其移植到糖尿病小鼠的腹膜后结肠后间隙。对照组小鼠将自由胰岛植入肾包膜下或包封胰岛植入腹腔。测量生化指标，并对移植的胰岛进行胰岛素和胰高血糖素免疫组织化学染色。
结果
接受植入腹膜后空间的包封大鼠、猪和人胰岛的小鼠，血糖中位数分别维持正常 275、145.5 和 146 天。相比之下，植入腹腔的包封异种胰岛分别维持功能中位数 61、95.5 和 82 天。同时，自由植入肾包膜下的异种胰岛在移植后 3 天内失去功能。从腹膜后空间取出的包封大鼠、猪和人胰岛的免疫组织化学染色允许分别在移植后 70、60 和 100 天区分形态正常的胰岛素表达β-和胰高血糖素表达α-细胞。
结论
Alg/PEI 包封异种胰岛移植到腹膜后空间为 1 型糖尿病的治疗提供了一种有价值的新植入策略。
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