No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques.
No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques.
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DOI：
10.1177/0963689721992066
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发表时间：
2021-01
影响因子：
3.3
通讯作者：
Ogasawara K
中科院分区：
文献类型：
--
作者：
Ishigaki H;Pham VL;Terai J;Sasamura T;Nguyen CT;Ishida H;Okahara J;Kaneko S;Shiina T;Nakayama M;Itoh Y;Ogasawara K
诱导多能干细胞(IPSCs)的致瘤性在IPSCs来源的细胞被移植时是可以预期的。有报道称，在没有免疫抑制的情况下，在非人灵长类动物模型中，iPSCs在体内形成了畸胎瘤。然而，目前还没有关于主要组织相容性复合体(MHC)相合的同种异体IPSC与免疫活性宿主移植致瘤性的研究。为了检测同种异体IPSC的致瘤性，我们产生了四个携带MHC纯合单倍型的IPSC克隆。其中两个克隆是用逆转录病毒从女性成纤维细胞获得的，另外两个克隆是用仙台病毒(Eisomal方法)从男性外周血单核细胞获得的。将IPSC克隆移植到MHC相合的同种异体免疫活性食蟹猴体内。在将IPSCs移植到一只MHC相合的雌性猕猴的皮下组织和两只MHC相合的雄性猕猴的四个睾丸中后，组织学分析显示，移植后3个月切除的组织中没有肿瘤、炎症或再生变化，尽管如先前报道的那样，IPSCs在免疫缺陷小鼠和自体移植中形成了畸胎瘤。本研究结果提示，在MHC相合的同种异体移植中，IPSCs在临床应用中不具有致瘤性。
Tumorigenicity of induced pluripotent stem cells (iPSCs) is anticipated when cells derived from iPSCs are transplanted. It has been reported that iPSCs formed a teratoma in vivo in autologous transplantation in a nonhuman primate model without immunosuppression. However, there has been no study on tumorigenicity in major histocompatibility complex (MHC)-matched allogeneic iPSC transplantation with immune-competent hosts. To examine the tumorigenicity of allogeneic iPSCs, we generated four iPSC clones carrying a homozygous haplotype of the MHC. Two clones were derived from female fibroblasts by using a retrovirus and the other two clones were derived from male peripheral blood mononuclear cells by using Sendai virus (episomal approach). The iPSC clones were transplanted into allogenic MHC-matched immune-competent cynomolgus macaques. After transplantation of the iPSCs into subcutaneous tissue of an MHC-matched female macaque and into four testes of two MHC-matched male macaques, histological analysis showed no tumor, inflammation, or regenerative change in the excised tissues 3 months after transplantation, despite the results that iPSCs formed teratomas in immune-deficient mice and in autologous transplantation as previously reported. The results in the present study suggest that there is no tumorigenicity of iPSCs in MHC-matched allogeneic transplantation in clinical application.
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影响因子：
8.8
作者：
Kondo, Takayuki;Imamura, Keiko;Inoue, Haruhisa
通讯作者：
Inoue, Haruhisa
MHC匹配改善了非人类灵长类动物中IPSC衍生的神经元的植入。
影响因子：
16.6
作者：
Morizane A;Kikuchi T;Hayashi T;Mizuma H;Takara S;Doi H;Mawatari A;Glasser MF;Shiina T;Ishigaki H;Itoh Y;Okita K;Yamasaki E;Doi D;Onoe H;Ogasawara K;Yamanaka S;Takahashi J
通讯作者：
Takahashi J
影响因子：
8.8
作者：
Hong SG;Winkler T;Wu C;Guo V;Pittaluga S;Nicolae A;Donahue RE;Metzger ME;Price SD;Uchida N;Kuznetsov SA;Kilts T;Li L;Robey PG;Dunbar CE
通讯作者：
Dunbar CE
iPS细胞及其分化衍生物的致瘤性
影响因子：
5.3
作者：
Liu Z;Tang Y;Lü S;Zhou J;Du Z;Duan C;Li Z;Wang C
通讯作者：
Wang C
影响因子：
4.4
作者：
Koch, Cody A.;Jordan, Corinne E.;Platt, Jeffrey L.
通讯作者：
Platt, Jeffrey L.