Kim Young-Tae, Bridge Michael J, Tresco Patrick A
The Keck Center for Tissue Engineering, Department of Bioengineering, College of Engineering, University of Utah, Salt Lake City, UT 84112, United States.
J Control Release. 2007 Apr 23;118(3):340-7. doi: 10.1016/j.jconrel.2007.01.002. Epub 2007 Jan 13.
The transplantation of genetically engineered fibroblasts has been shown to be an effective approach for achieving continuous and site-specific delivery of therapeutic molecules to various regions of the central nervous system. However, to our knowledge no one has asked whether soluble factors released from the transplanted fibroblasts influence the delivery of therapeutic molecules from the engrafted cells. To address this issue, we used a newly developed cell encapsulation device to study the functional consequence of the foreign body response on soluble factor delivery from fibroblasts transplanted into adult brain tissue. We found that transplanted fibroblasts increased the level of inflammation and glial cell encapsulation at the transplantation site, and reduced the diffusion of a 70 kDa dextran probe through the reactive tissue. The response, however, did not prevent the diffusion of the 70 kDa dextran test probe indicating that the approach appears suitable for the delivery of neurotrophins and other therapeutic molecules with a molecular weight less than 70 kDa. The results suggest that less reactive cell types may be better suited for sustained delivery of therapeutic molecules into brain tissue.
基因工程成纤维细胞的移植已被证明是一种有效的方法，可实现治疗性分子向中枢神经系统各个区域的持续和位点特异性递送。然而，据我们所知，没有人问过移植的成纤维细胞释放的可溶性因子是否会影响植入细胞中治疗性分子的递送。为了解决这个问题，我们使用了一种新开发的细胞封装装置来研究异物反应对移植到成年脑组织中的成纤维细胞可溶性因子递送的功能影响。我们发现，移植的成纤维细胞增加了移植部位的炎症水平和胶质细胞封装，并减少了70 kDa葡聚糖探针通过反应性组织的扩散。然而，这种反应并没有阻止70 kDa葡聚糖测试探针的扩散，这表明该方法似乎适用于递送神经营养因子和其他分子量小于70 kDa的治疗性分子。结果表明，反应性较低的细胞类型可能更适合将治疗性分子持续递送至脑组织。
