Sakurai Tomonori, Satake Akira, Sumi Shoichiro, Inoue Kazutomo, Nagata Natsuki, Tabata Yasuhiko, Miyakoshi Junji
Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Pancreas. 2004 Apr;28(3):e70-9. doi: 10.1097/00006676-200404000-00028.
The subcutaneous transplantation of a bioartificial pancreas is a very attractive cure for diabetes mellitus. We recently developed a new immunoisolatory device that has the ability to induce neovascularization for subcutaneous transplantation. We applied the newly developed device to subcutaneous transplantation of a bioartificial pancreas.
We investigated the prevascularization-inducing activity of the device in diabetic rats by histologic analysis and evaluated the permeability of the device to insulin and BSA. We also evaluated the survival of cells enclosed in a bioartificial pancreas, which was composed of the device, from the viewpoint of the effects of prevascularization by semiquantitative RT-PCR.
The devices induced prevascularization more efficiently than fibroblast growth factor 2 impregnated in gelatin microspheres alone did and had more useful permeability than a noncollagen-coated device. Significantly higher expression of insulin mRNA was detected in the RT-PCR amplicons from cells retrieved from the bioartificial pancreas transplanted at the prevascularization-induced site as compared with at a nonprevascularization-induced site.
We demonstrated that our newly developed device has a superior ability to induce prevascularization in diabetic rats, and the prevascularization improves the initial cell survival of the implanted cells following transplantation.
生物人工胰腺的皮下移植是一种非常有吸引力的糖尿病治疗方法。我们最近开发了一种新的免疫隔离装置,其具有诱导皮下移植新生血管形成的能力。我们将新开发的装置应用于生物人工胰腺的皮下移植。
我们通过组织学分析研究了该装置在糖尿病大鼠中的促血管生成活性,并评估了该装置对胰岛素和牛血清白蛋白的通透性。我们还从半定量逆转录聚合酶链反应(RT-PCR)检测的促血管生成作用的角度,评估了由该装置组成的生物人工胰腺中包裹细胞的存活情况。
与单独包埋在明胶微球中的成纤维细胞生长因子2相比,该装置能更有效地诱导血管生成,并且与未包被胶原蛋白的装置相比,具有更有利的通透性。与未诱导血管生成的部位相比,在诱导血管生成部位移植的生物人工胰腺中回收的细胞的RT-PCR扩增产物中检测到胰岛素mRNA的表达明显更高。
我们证明了新开发的装置在糖尿病大鼠中具有卓越的诱导血管生成能力,并且血管生成改善了移植后植入细胞的初始细胞存活情况。