Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering
Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering
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大鼠模型中的同种异体肝移植和随后的同基因肝细胞移植：体内组织工程的概念验证
DOI：
10.1159/000445792
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发表时间：
2015
影响因子：
2.7
通讯作者：
Mogl MT
中科院分区：
文献类型：
--
作者：
Rohn S;Schröder J;Riedel H;Polenz D;Stanko K;Reutzel-Selke A;Tang P;Brusendorf L;Raschzok N;Neuhaus P;Pratschke J;Sawitzki B;Sauer IM;Mogl MT
目的人类肝细胞移植后长期稳定的功能仍然没有成功实现。一种新的肝细胞成功植入的方法可能是将同基因细胞移植到同种异体肝移植物中。因此，我们开发了一种新的大鼠模型联合肝脏和肝细胞移植（cLCTx）下稳定immunosuppress.Materials和MethodsAfter诱导有丝分裂阻滞，肝移植从雌性供体大鼠（黑Aggilli）移植到女性受体（刘易斯）。在雄性刘易斯大鼠中，诱导肝细胞增殖，随后进行细胞分离并在器官移植后移植到雌性受体中。Y-染色体检测的移植的雄性细胞进行定量聚合酶链反应（qPCR）和荧光原位杂交（FisH）与本地化的移植细胞通过immunohistochemistry.ResultsImmunohistochemistry证明移植细胞的植入，确认FisH，显示再增殖的肝移植物与15.6%的男性细胞（±1.8 SEM）在第90天。qPCR检测结果显示，cLCTx后90 d内有14.15%（± 5.09SEM）的雄性DNA。结论在免疫抑制条件下，cLCTx后移植的同基因细胞可持续植入90 d。免疫组织化学显示细胞增殖，并且FisH结果通过qPCR部分证实。在大鼠中的这种新方案对于解决长期功能和最终在未来诱导操作耐受似乎是可行的。
ObjectivesStable long-term functioning of liver cells after transplantation in humans is still not achieved successfully. A new approach for successful engraftment of liver cells may be the transplantation of syngeneic cells into an allogeneic liver graft. We therefore developed a new rat model for combined liver and liver cell transplantation (cLCTx) under stable immunosuppression.Materials and MethodsAfter inducing a mitotic block, liver grafts from female donor rats (Dark Agouti) were transplanted into female recipients (Lewis). In male Lewis rats, liver cell proliferation was induced with subsequent cell isolation and transplantation into female recipients after organ transplantation. Y-chromosome detection of the transplanted male cells was performed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FisH) with localization of transplanted cells by immunohistochemistry.ResultsImmunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by FisH, showing repopulation of the liver graft with 15.6% male cells (±1.8 SEM) at day 90. qPCR revealed 14.15%(±5.09 SEM) male DNA at day 90.ConclusionEngraftment of transplanted syngeneic cells after cLCTx was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the FisH results were partly confirmed by qPCR. This new protocol in rats appears feasible for addressing long-term functioning and eventually the induction of operational tolerance in the future.
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影响因子：
56.9
作者：
RHIM, JA;SANDGREN, EP;BRINSTER, RL
通讯作者：
BRINSTER, RL
影响因子：
25.7
作者：
Soltys KA;Soto-Gutiérrez A;Nagaya M;Baskin KM;Deutsch M;Ito R;Shneider BL;Squires R;Vockley J;Guha C;Roy-Chowdhury J;Strom SC;Platt JL;Fox IJ
通讯作者：
Fox IJ
大鼠肝移植：单中心技术经验、长期生存以及功能和组织学发现。
影响因子：
0.9
作者：
E. Matevossian;D. Doll;N. Hüser;R. Brauer;I. Sinicina;J. Nährig;H. Friess;M. Stangl;V. Assfalg
通讯作者：
V. Assfalg
影响因子：
3.1
作者：
Miyaso, Hideaki;Morimoto, Yoshinori;Iwagaki, Hiromi
通讯作者：
Iwagaki, Hiromi
影响因子：
0.9
作者：
S. C. Strom;R. Fisher;W. Rubinstein;J. Barranger;R. Towbin;M. Charron;L. Mieles;L. Pisarov;K. Dorko;M. Thompson;J. Reyes
通讯作者：
J. Reyes