Human embryonic stem cells are prone to generate primitive, undifferentiated tumors in engrafted human fetal tissues in severe combined immunodeficient mice
Human embryonic stem cells are prone to generate primitive, undifferentiated tumors in engrafted human fetal tissues in severe combined immunodeficient mice
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DOI：
10.1089/scd.2007.0070
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发表时间：
2007-12-01
影响因子：
4
通讯作者：
Slovak, Marilyn
中科院分区：
文献类型：
--
作者：
Shih, Chu-Chih;Forman, Stephen J.;Slovak, Marilyn
胚胎干细胞（ES）具有独特的自我更新能力和产生所有可能细胞类型的潜力。它们的分化潜力带来了希望，即这些细胞可用作严重退行性疾病细胞移植的可再生来源。然而，这方面的进展仍然有限。利用两种人胚胎干细胞系HI和HSF-6以及三种人胎儿组织-胸腺、肺和胰腺-研究了人胎儿组织移植到严重联合免疫缺陷小鼠（SCID）体内是否能为人胚胎干细胞分化为相应组织的成熟细胞提供生理相关的微环境。令人惊讶的是，当将人ES细胞注射到植入的细胞中时，我们观察到肿瘤的侵袭性生长。SCID小鼠中的人胎儿组织。这些肿瘤显示原始的，未分化的肿瘤，而不是分化畸胎瘤的组织学特征。此外，这些肿瘤表现出正常的核型，不表达胚胎癌的特征性抗原。我们还发现不同类型的人类胎儿组织支持这些原始肿瘤生长的能力存在差异。我们的研究支持并验证了先前报道的小鼠ES细胞的肿瘤发生是宿主依赖性的现象。我们的研究也是第一份证明人ES细胞易于在SCID小鼠的人胎儿组织移植物中产生原始未分化肿瘤的报告，并提出了在人体中使用人ES细胞衍生的细胞产品的潜在安全性问题。
Embryonic stem (ES) cells are uniquely endowed with the capacity of self-renewal and the potential to give rise to all possible cell types. Their dirferentiation potential has raised hope that these cells could be used as a renewable source for cell transplantation in severe degenerative diseases. However, progress in this direction is still limited. Using two human embryonic stem (ES) cell lines, HI and HSF-6, and three types of human fetal tissues-thymus, lung and pancreas-we investigated whether engrafted human fetal tissues in severe combined immunodeficient mice (SCID) mice could provide a physiologically-relevant microenvironment for human ES cells to differentiate into mature cells of corresponding tissues. Surprisingly, we observed an aggressive growth of tumors when human ES cells were injected into engrafted. human fetal tissues in SCID mice. These tumors displayed histological characteristics of primitive, undifferentiated tumors rather than differentiated teratomas. Additionally, these tumors exhibited a normal karyotype and did not express the characteristic antigens of embryonic carcinomas. We also found differences among human fetal tissue types in their abilities to support the growth or these primitive tumors. Our study supports and validates a previously reported phenomenon in mouse that tumorigenesis of ES cells is host dependent. Our study is also the first report to demonstrate that human ES cells are prone to generate primitive, undifferentiated tumors in human fetal tissue grafts in SCID mice and raises a potential safety concern for using human ES cell-derived cell products in humans.