碩士 / 國立臺灣大學 / 分子醫學研究所 / 90 / The organ transplantation is able to rescue the organ failure. However, the adverse effects of the immunosuppressants, such as hepatotoxicity, myelotoxicity and pancreatic toxicity offset the benefits of transplantation. Since the supply of human organ is limited for organ transplantation, microencapsulation of cell grafts has been proposed as an alternative to life long immunosuppression for prevention of graft rejection and autoimmune destruction. Alginate-poly-L-lysine-alginate (A-P-A) microencapsulation is a promising technique for transgenic cell, stem cell, allogeneic cell, xenogeneic cell from transgenic animal and other endocrine cell transplantation.
In our experiment, 2000-3000 intraperitoneally implanted A-P-A microencapsulated rat islets reversed hyperglycemia of streptozotocin (STZ)-induced diabetic mouse for up to 4 months. It was noted that the surface of retrieved microcapsules had marked neogrowth and most of the cellular components were macrophages and fibroblasts. Since empty A-P-A microcapsules retrieved 6 months after implantation had no surface neogrowth, the growth of macrophages and fibroblasts over capsular surface was thought to be graft-related. The failure of transplantation may be attributed to the presence of macrophages on the capsular surface.
Immunomodulators including interleukin-1 receptor antagonist (IL-1ra) and cytotoxic T lymphocyte antigen-4 with Fc portion of human immunoglobulin fusion protein (CTLA-4Ig) are able to block suppressive effect of IL-1β and D28-B7 costimulatory pathway and to prolong islet graft survival. A macrophage inhibitor, 15-deoxyspergualin (DSG), has a rescue effect on the rejected intraperitoneal A-P-A microencapsulated rat islets. The rescue effect of 15-DSG is possibly mediated via both of its inhibitory effect on peritoneal adherent macrophage and its suppressive effect on interleukin-1 beta (IL-1β) gene expression of intraperitoneal mononuclear cells of diabetic BALB/c mice. Our data showed that inhibition of macrophage activity and ability to release cytokines could effectively prolong survival time of microencapsulated islets.
| Identifer | oai:union.ndltd.org:TW/090NTU01538003 |
| Date | January 2002 |
| Creators | Shin-Huei Fu, 傅馨慧 |
| Contributors | Chia-Li Yu, 余家利 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 0 |
Page generated in 0.0074 seconds