B-cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months.
B-cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months.
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DOI：
10.1111/j.1600-6143.2011.03846.x
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Horvath KA
中科院分区：
文献类型：
--
作者：
Mohiuddin MM;Corcoran PC;Singh AK;Azimzadeh A;Hoyt RF Jr;Thomas ML;Eckhaus MA;Seavey C;Ayares D;Pierson RN 3rd;Horvath KA
转基因猪器官的异种移植为解决人类同种异体移植器官短缺问题提供了巨大的潜力。由于引发的非Gal抗体应答，Gal KO猪中超急性排斥反应的持续性需要供体猪的进一步遗传修饰和对异种抗原的B细胞应答的更好控制。我们报告了在已建立的抗CD154和霉酚酸酯免疫抑制方案中加入移植物周围B细胞耗竭后，移植物存活时间显著延长8个月。具体而言，将半乳糖基转移酶“敲除”和人CD46转基因（GTKO.CD46Tg）猪心脏异种移植物异位移植到无特定病原体（SPF）狒狒中。仅用抗CD 20抗体诱导治疗4次后，B细胞数量和非Gal抗体产生仍被抑制超过2个月。通过遥测技术对移植心脏和受体进行连续评估，可准确评估移植物功能并辅助术后护理，从而预防几种主要并发症。加入抗CD 20抗体后移植物存活率的显著差异确定了B细胞在延迟性异种移植排斥机制中的关键作用，并代表了临床应用的显著进展。
Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Persistence of hyperacute rejection in Gal KO pigs due to elicited non Gal antibody response required further genetic modifications of donor pigs and better control of the B cell response to xeno antigens. We report significant prolongation of graft survival of 8 months when peri-transplant B-cell depletion was added to an established anti CD154 and MMF based immunosuppressive regimen. Specifically Galactosyl transferase “knock-out” and human CD46 transgenic (GTKO.CD46Tg) pig cardiac xenografts were heterotopically transplanted into specific pathogen free (SPF) baboons. The B cell numbers and non Gal antibody production remained suppressed for over 2 months after only 4 doses of induction treatment with an anti CD20 antibody. Continuous evaluation of the transplanted hearts and recipients by telemetry provided accurate assessment of graft function and aided post operative care, allowing prevention of several major complications. The significant difference in graft survival with the addition of anti CD20 antibody identifies a critical role for B cells in the mechanisms of delayed xenograft rejection and represents a significant advance toward clinical application.
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影响因子：
0.9
作者：
Corcoran, P. C.;Horvath, K. A.;Mohiuddin, M. M.
通讯作者：
Mohiuddin, M. M.
影响因子：
6
作者：
Shimizu, Akira;Hisashi, Yosuke;Colvin, Robert B.
通讯作者：
Colvin, Robert B.
影响因子：
1.6
作者：
Sandrin, MS;Loveland, BE;McKenzie, IFC
通讯作者：
McKenzie, IFC
影响因子：
3.9
作者：
Loveland, BE;Milland, J;McKenzie, IFC
通讯作者：
McKenzie, IFC
影响因子：
3.9
作者：
Nguyen, Bao-Ngoc H.;Azimzadeh, Agnes M.;Pierson, Richard N., III
通讯作者：
Pierson, Richard N., III