Bone marrow as an alternative site for islet transplantation
Bone marrow as an alternative site for islet transplantation
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DOI：
10.1182/blood-2009-03-209973
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发表时间：
2009-11-12
期刊：
影响因子：
20.3
通讯作者：
Piemonti, Lorenzo
中科院分区：
文献类型：
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作者：
Cantarelli, Elisa;Melzi, Raffaella;Piemonti, Lorenzo
肝脏是目前胰岛移植的主要部位，但由于免疫和非免疫因素的影响，肝脏移植存在许多缺陷。我们询问胰岛是否可以移植到骨髓（BM）中，骨髓是一个容易获得和广泛分布的移植部位，可能没有肝脏中看到的限制。同基因胰岛有效地移植到C57 BL/6小鼠的骨髓中，通过链脲佐菌素治疗使其患糖尿病。移植后1年以上，这些动物显示出与非糖尿病小鼠相似的葡萄糖代谢参数。BM中的胰岛比肝脏中的胰岛有更高的概率达到正常水平（增加2.4倍，P = 0.02），显示出紧凑的形态，α和β细胞之间的比例保守，对骨结构的影响非常轻微。骨髓中的胰岛不损害造血活性，即使是在骨髓再生障碍诱导感染淋巴细胞性脉络丛脑膜炎病毒时强烈诱导。总之，骨髓是一个有吸引力的和安全的替代网站胰岛移植。我们的研究结果开辟了一条具有潜在重大临床影响的研究路线，不仅用于治疗糖尿病，而且用于其他适合细胞移植治疗的疾病。（血。2009; 114：4566-4574）
The liver is the current site for pancreatic islet transplantation, but has many drawbacks due to immunologic and nonimmunologic factors. We asked whether pancreatic islets could be engrafted in the bone marrow ( BM), an easily accessible and widely distributed transplant site that may lack the limitations seen in the liver. Syngeneic islets engrafted efficiently in the BM of C57BL/6 mice rendered diabetic by streptozocin treatment. For more than 1 year after transplantation, these animals showed parameters of glucose metabolism that were similar to those of nondiabetic mice. Islets in BM had a higher probability to reach euglycemia than islets in liver (2.4-fold increase, P = .02), showed a compact morphology with a conserved ratio between alpha and beta cells, and affected bone structure only very marginally. Islets in BM did not compromise hematopoietic activity, even when it was strongly induced in response to a BM aplasia-inducing infection with lymphocytic choriomeningitis virus. In conclusion, BM is an attractive and safe alternative site for pancreatic islet transplantation. The results of our study open a research line with potentially significant clinical impact, not only for the treatment of diabetes, but also for other diseases amenable to treatment with cellular transplantation. ( Blood. 2009; 114: 4566-4574)