Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
Transplantation. 2010 Sep 27;90(6):604-11. doi: 10.1097/TP.0b013e3181ca64d1.
Fibrous tissue outgrowth and hypoxia are the major restrictions for the application of bioartificial pancreas (BAP). Accordingly, the intramedullary cavity is proposed as an implant site, and a BAP constructed of calcium phosphate cement chamber was implanted.
Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a calcium phosphate cement chamber to fabricate a BAP. BAPs were implanted in the femoral intramedullary cavity of diabetic dogs. Pre- and postprandial blood glucose levels were monitored perioperatively. Blood samples were collected for the analysis of C-peptide level, and physiological conditions were observed at predetermined intervals. BAPs were retrieved at 12 weeks postoperatively for histologic examination.
Preprandial blood glucose level of diabetic dogs decreased from 420 ± 25 to 223 ± 47 mg/dL at 1 day postoperatively and was maintained in the range of 259 ± 36 mg/dL for 12 weeks. As serum C-peptide level increased from 5.3 ± 2.8 to 105.7 ± 19.4 pmol/L, the rate of decrease of postprandial blood glucose was accelerated. Histologic examination revealed that recipient bone tissues were binding to the surfaces of BAPs directly; there was no development of fibrous tissue. Immunohistochemical stain was positive for insulin in the enclosed insulinoma cells.
This study demonstrated that BAPs implanted into the intramedullary cavity functioned well during the experimental period. Thus, the intramedullary cavity can serve as an implant site for BAPs.
纤维组织增生和缺氧是生物人工胰腺(BAP)应用的主要限制因素。因此,骨髓腔被提议作为植入部位,并植入了由磷酸钙水泥室构建的 BAP。
将小鼠胰岛素瘤细胞包埋在琼脂糖凝胶中,然后包裹在磷酸钙水泥室中,以制备 BAP。将 BAP 植入糖尿病犬的股骨髓腔内。在手术前后监测餐前和餐后血糖水平。采集血样分析 C 肽水平,并在预定间隔观察生理状况。术后 12 周取回 BAP 进行组织学检查。
糖尿病犬的餐前血糖水平从 420±25mg/dL 降低到术后 1 天的 223±47mg/dL,并在 12 周内维持在 259±36mg/dL 的范围内。随着血清 C 肽水平从 5.3±2.8pmol/L 增加到 105.7±19.4pmol/L,餐后血糖的下降速度加快。组织学检查显示,受者骨组织直接与 BAP 表面结合;没有纤维组织的发展。封闭的胰岛素瘤细胞中的胰岛素免疫组织化学染色呈阳性。
本研究表明,植入骨髓腔的 BAP 在实验期间功能良好。因此,骨髓腔可以作为 BAP 的植入部位。