Lessons from human teratomas to guide development of safe stem cell therapies
Lessons from human teratomas to guide development of safe stem cell therapies
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DOI：
10.1038/nbt.2329
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发表时间：
2012-09-01
影响因子：
46.9
通讯作者：
Looijenga, Leendert H. J.
中科院分区：
文献类型：
--
作者：
Cunningham, Justine J.;Ulbright, Thomas M.;Looijenga, Leendert H. J.
畸胎瘤或其他肿瘤的潜在形成是多能干细胞疗法临床应用的主要安全障碍。在这种情况下，对肿瘤形成风险的临床前评估提出了相当大的科学和监管挑战，特别是因为动物异种移植模型可能不能正确反映人类细胞的长期致瘤潜力。更好地了解人类自发发生的畸胎瘤和相关肿瘤的生物学有助于指导评估和减少胚胎干细胞或诱导多能干细胞疗法的潜在危险的努力。在这里，我们回顾了实验上来源于人类多能干细胞的畸胎瘤的特征，并认为它们与早期发生在小鼠和人类生命中的自发性良性畸胎瘤最为相似。这些自发发生的畸胎瘤的自然病史和病理学为干细胞治疗试验中的临床前安全性评估和患者监测提供了重要线索。
The potential for the formation of teratomas or other neoplasms is a major safety roadblock to clinical application of pluripotent stem cell therapies. Preclinical assessment of the risk of tumor formation in this context poses considerable scientific and regulatory challenges, especially because animal xenograft models may not properly reflect the long-term tumorigenic potential of human cells. A better understanding of the biology of spontaneously occurring teratomas and related tumors in humans can help to guide efforts to assess and minimize the potential hazards of embryonic stem cell or induced pluripotent stem cell therapeutics. Here we review the features of teratomas derived experimentally from human pluripotent stem cells and argue that they most closely resemble spontaneous benign teratomas that occur early in both mouse and human life. The natural history and pathology of these spontaneously occurring teratomas provide important clues for preclinical safety assessment and patient monitoring in trials of stem cell therapies.