Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
Pancreas. 2010 May;39(4):444-51. doi: 10.1097/MPA.0b013e3181be2f95.
This study examined a calcium phosphate cement (CPC) chamber as an immunoisolative device to facilitate the use of xenogeneic cell sources without immunosuppression for the bioartificial pancreas (BAP).
Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a CPC chamber to create a BAP. Bioartificial pancreas were evaluated by cell viability, live-dead cell ratio, and cytokine-mediated cytotoxicity assay and implanted into the peritoneal cavity of diabetic rats. Nonfasting blood glucose and serum insulin levels were analyzed perioperatively; BAPs were also retrieved for histological examination.
Insulinoma cells enclosed in the CPC chamber had normal viability, cell survival, and insulin secretion that was even cultured in media with cytokines. The nonfasting blood glucose level of rats was decreased from 460 +/- 50 to 132 +/- 43 mg/dL and maintained euglycemia for 22 days; serum insulin level was increased from 0.34 +/- 0.11 to 1.43 +/- 0.30 microg/dL after operation. Histological examination revealed the fibrous tissue envelopment, and immune-related cells that competed for oxygen resulting in hypoxia could be attributed to the dysfunction of BAPs.
This study proved the feasibility for using a CPC chamber as an immunoisolative device for the BAP. An alternative implanted site should be considered to extend the functional longevity of BAPs in further study.
本研究探讨了磷酸钙水泥（CPC）室作为免疫隔离装置，以促进在不使用免疫抑制的情况下使用异种细胞源来构建生物人工胰腺（BAP）。
将小鼠胰岛素瘤细胞包埋在琼脂糖凝胶中，然后封闭在 CPC 室中以构建 BAP。通过细胞活力、活细胞与死细胞比例以及细胞因子介导的细胞毒性测定来评估生物人工胰腺，并将其植入糖尿病大鼠的腹腔内。分析手术前后的非禁食血糖和血清胰岛素水平；还检索 BAP 进行组织学检查。
在 CPC 室内包封的胰岛素瘤细胞具有正常的活力、细胞存活和胰岛素分泌功能，即使在含有细胞因子的培养基中培养也是如此。大鼠的非禁食血糖水平从 460±50 降至 132±43 mg/dL，并维持了 22 天的正常血糖水平；术后血清胰岛素水平从 0.34±0.11 增至 1.43±0.30 microg/dL。组织学检查显示纤维组织包裹和免疫相关细胞争夺氧气导致缺氧，这可能是 BAP 功能障碍的原因。
本研究证明了使用 CPC 室作为 BAP 的免疫隔离装置的可行性。在进一步的研究中，应该考虑替代植入部位，以延长 BAP 的功能寿命。
