Controlling immune rejection is a fail-safe system against potential tumorigenicity after human iPSC-derived neural stem cell transplantation.
Controlling immune rejection is a fail-safe system against potential tumorigenicity after human iPSC-derived neural stem cell transplantation.
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DOI：
10.1371/journal.pone.0116413
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nakamura M
中科院分区：
文献类型：
--
作者：
Itakura G;Kobayashi Y;Nishimura S;Iwai H;Takano M;Iwanami A;Toyama Y;Okano H;Nakamura M
我们之前的工作报道了小鼠和人诱导多能干细胞衍生的神经干细胞/祖细胞（hiPSC-NS/PCs）移植到啮齿动物脊髓损伤（SCI）模型后功能恢复。尽管hiPSC-NS/PCs被证明对脊髓损伤的治疗是有用的，但移植细胞的致瘤性必须在它们用于临床应用之前得到解决。目前的研究旨在通过免疫调节确定hiPSC-NS/PC移植后形成的肿瘤消融的可行性。将致瘤性hiPSC-NS/PCs移植到免疫功能正常的BALB/cA小鼠的完整脊髓中，并给予或不给予免疫抑制剂治疗。体内生物发光成像用于评估移植细胞的时间顺序存活和生长。无免疫抑制剂组的移植存活率为0%，而有免疫抑制剂组的移植存活率为100%。大多数接受免疫抑制剂的小鼠在iPSC-NS/PC移植后3个月由于肿瘤生长而出现后肢瘫痪。组织学分析显示肿瘤与低级别胶质瘤而非畸胎瘤具有某些共同特征。在确认免疫抑制小鼠的肿瘤进展后，停用免疫抑制剂，导致停药后42天内iPSC-NS/ pc来源的肿块完全排斥。与肿瘤排斥反应一致，所有小鼠后肢运动功能均恢复。此外，在肿瘤排斥过程中观察到小胶质细胞和淋巴细胞的浸润，同时iPSC-NS/ pc生成的细胞凋亡。因此，在移植iPSC-NS/PCs治疗脊髓损伤后，免疫排斥反应可以作为一种故障安全系统来对抗潜在的致瘤性。
Our previous work reported functional recovery after transplantation of mouse and human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) into rodent models of spinal cord injury (SCI). Although hiPSC-NS/PCs proved useful for the treatment of SCI, the tumorigenicity of the transplanted cells must be resolved before they can be used in clinical applications. The current study sought to determine the feasibility of ablation of the tumors formed after hiPSC-NS/PC transplantation through immunoregulation. Tumorigenic hiPSC-NS/PCs were transplanted into the intact spinal cords of immunocompetent BALB/cA mice with or without immunosuppressant treatment. In vivo bioluminescence imaging was used to evaluate the chronological survival and growth of the transplanted cells. The graft survival rate was 0% in the group without immunosuppressants versus 100% in the group with immunosuppressants. Most of the mice that received immunosuppressants exhibited hind-limb paralysis owing to tumor growth at 3 months after iPSC-NS/PC transplantation. Histological analysis showed that the tumors shared certain characteristics with low-grade gliomas rather than with teratomas. After confirming the progression of the tumors in immunosuppressed mice, the immunosuppressant agents were discontinued, resulting in the complete rejection of iPSC-NS/PC-derived masses within 42 days after drug cessation. In accordance with the tumor rejection, hind-limb motor function was recovered in all of the mice. Moreover, infiltration of microglia and lymphocytes was observed during the course of tumor rejection, along with apoptosis of iPSC-NS/PC-generated cells. Thus, immune rejection can be used as a fail-safe system against potential tumorigenicity after transplantation of iPSC-NS/PCs to treat SCI.
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DOI：
10.1159/000099279
发表时间：
2007-01-01
期刊：
Chemical immunology and allergy
影响因子：
--
作者：
Hori, Junko;Niederkorn, Jerry Y
通讯作者：
Niederkorn, Jerry Y
DOI：
10.1093/brain/awr339
发表时间：
2012-02
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Cusimano M;Biziato D;Brambilla E;Donegà M;Alfaro-Cervello C;Snider S;Salani G;Pucci F;Comi G;Garcia-Verdugo JM;De Palma M;Martino G;Pluchino S
通讯作者：
Pluchino S
影响因子：
1.2
作者：
Akesson, Elisabet;Wolmer-Solberg, Nina;Odeberg, Jenny
通讯作者：
Odeberg, Jenny
DOI：
10.1056/nejmoa1106152
发表时间：
2011-11-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Di Stasi A;Tey SK;Dotti G;Fujita Y;Kennedy-Nasser A;Martinez C;Straathof K;Liu E;Durett AG;Grilley B;Liu H;Cruz CR;Savoldo B;Gee AP;Schindler J;Krance RA;Heslop HE;Spencer DM;Rooney CM;Brenner MK
通讯作者：
Brenner MK
影响因子：
9
作者：
Dressel, Ralf
通讯作者：
Dressel, Ralf