Cantarelli Elisa, Melzi Raffaella, Mercalli Alessia, Sordi Valeria, Ferrari Giuliana, Lederer Carsten Werner, Mrak Emanuela, Rubinacci Alessandro, Ponzoni Maurilio, Sitia Giovanni, Guidotti Luca G, Bonifacio Ezio, Piemonti Lorenzo
San Raffaele Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy.
Blood. 2009 Nov 12;114(20):4566-74. doi: 10.1182/blood-2009-03-209973. Epub 2009 Sep 22.
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.
肝脏是目前胰岛移植的部位，但由于免疫和非免疫因素存在诸多缺点。我们探讨了胰岛是否可以移植到骨髓（BM）中，骨髓是一个易于获取且分布广泛的移植部位，可能不存在肝脏移植中所见的局限性。同基因胰岛能有效地移植到经链脲佐菌素处理而致糖尿病的C57BL/6小鼠的骨髓中。移植后1年多，这些动物的葡萄糖代谢参数与非糖尿病小鼠相似。骨髓中的胰岛达到血糖正常的概率高于肝脏中的胰岛（增加2.4倍，P = 0.02），呈现紧密的形态，α细胞和β细胞之间的比例保持不变，对骨结构的影响微乎其微。骨髓中的胰岛不会损害造血活性，即使在因淋巴细胞性脉络丛脑膜炎病毒诱导骨髓再生障碍的感染而强烈诱导造血活性时也是如此。总之，骨髓是胰岛移植的一个有吸引力且安全的替代部位。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，还可用于其他适合细胞移植治疗的疾病。
