Path to the clinic: assessment of iPSC-based cell therapies in vivo in a nonhuman primate model.
Path to the clinic: assessment of iPSC-based cell therapies in vivo in a nonhuman primate model.
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DOI：
10.1016/j.celrep.2014.04.019
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发表时间：
2014-05-22
期刊：
影响因子：
8.8
通讯作者：
Dunbar CE
中科院分区：
文献类型：
--
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
基于诱导多能干细胞（iPSC）的细胞疗法在再生医学方面具有巨大潜力，但也可能与致瘤风险相关。目前的啮齿动物模型不是临床应用的有效性和安全性的最佳预测因子。因此，我们开发了一种临床相关的非人灵长类动物模型，以评估未分化和分化的iPSC在无免疫抑制的自体环境中的致瘤潜力和体内功效。未分化的自体iPSC确实以剂量依赖性方式形成成熟畸胎瘤。然而，肿瘤形成伴随着炎症反应。另一方面，iPSC衍生的中胚层基质样细胞在体内形成新骨，而没有任何畸胎瘤形成的证据。因此，我们首次在与人类生理学非常相似的大型动物模型中显示，未分化的自体iPSC形成畸胎瘤，并且iPSC衍生的祖细胞可以在体内产生功能组织。
Induced pluripotent stem cell (iPSC)-based cell therapies have a great potential for regenerative medicine, but are also potentially associated with tumorigenic risks. Current rodent models are not the optimal predictors of efficiency and safety for clinical application. Therefore, we developed a clinically relevant non-human primate model to assess the tumorigenic potential and in vivo efficacy of both undifferentiated and differentiated iPSCs in the autologous settings without immunosuppression. Undifferentiated autologous iPSCs indeed formed mature teratomas in a dose-dependent manner. However, tumor formation was accompanied by an inflammatory reaction. On the other hand, iPSC-derived mesodermal stromal-like cells formed new bone in vivo without any evidence of teratoma formation. We therefore show for the first time in a large animal model that closely resembles human physiology that undifferentiated autologous iPSCs form teratomas, and that iPSC-derived progenitor cells can give rise to a functional tissue in vivo.
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影响因子：
8.8
作者：
Emborg ME;Liu Y;Xi J;Zhang X;Yin Y;Lu J;Joers V;Swanson C;Holden JE;Zhang SC
通讯作者：
Zhang SC
影响因子：
2.7
作者：
Okita, Keisuke;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
影响因子：
46.9
作者：
Cunningham, Justine J.;Ulbright, Thomas M.;Looijenga, Leendert H. J.
通讯作者：
Looijenga, Leendert H. J.
影响因子：
5.2
作者：
Bilousova, Ganna;Jun, Du Hyun;King, Karen B.;De Langhe, Stijn;Chick, Wallace S.;Torchia, Enrique C.;Chow, Kelsey S.;Klemm, Dwight J.;Roop, Dennis R.;Majka, Susan M.
通讯作者：
Majka, Susan M.
DOI：
10.1073/pnas.1201830109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Marolt, Darja;Campos, Ivan Marcos;Vunjak-Novakovic, Gordana
通讯作者：
Vunjak-Novakovic, Gordana