Improved Safety of Hematopoietic Transplantation with Monkey Embryonic Stem Cells in the Allogeneic Setting
Improved Safety of Hematopoietic Transplantation with Monkey Embryonic Stem Cells in the Allogeneic Setting
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DOI：
10.1634/stemcells.2005-0391
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发表时间：
2006-06
期刊：
影响因子：
5.2
通讯作者：
H. Shibata;N. Ageyama;Yujiro Tanaka;Y. Kishi;K. Sasaki;Shin'ichiro Nakamura;S. Muramatsu;S. Hayashi;Y. Kitano;K. Terao;Y. Hanazono
中科院分区：
文献类型：
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作者：
H. Shibata;N. Ageyama;Yujiro Tanaka;Y. Kishi;K. Sasaki;Shin'ichiro Nakamura;S. Muramatsu;S. Hayashi;Y. Kitano;K. Terao;Y. Hanazono
在同种异体移植模型中，研究了食蟹猴胚胎干细胞(CyESC)在体内的造血活性。体外诱导CyESCs分化为造血祖细胞，并在妊娠早期(n=3)将其移植到食蟹猴的胎肝内。尽管在新生儿中检测到CyESC来源的造血祖细胞(4.1%-4.7%)，但所有新生儿都发生了畸胎瘤。在这种同种异体移植模型中，肿瘤形成的风险很高，因为在免疫缺陷小鼠或胎羊身上几乎没有观察到肿瘤的形成，这些小鼠或胎羊已经被移植了相同的cyESC衍生物。结果表明，尽管经过严格的分化培养，cyESC来源的供体细胞仍含有阶段特异性胚胎抗原(SSEA)-4阳性的未分化残留物(38.2%±10.3%)。当移植SSEA-4阴性组分时(n=6)，畸胎瘤不再出现，而cyESC来源的造血植入未受干扰(2.3%-5.0%)。因此，SSEA-4是灵长类胚胎干细胞(ESCs)的一种具有临床意义的多能性标志物。用这种表面标记净化多能细胞将是一种利用人胚胎干细胞生产临床祖细胞制剂的有前途的方法。
Cynomolgus monkey embryonic stem cell (cyESC)‐derived in vivo hematopoiesis was examined in an allogeneic transplantation model. cyESCs were induced to differentiate into the putative hematopoietic precursors in vitro, and the cells were transplanted into the fetal cynomolgus liver at approximately the end of the first trimester (n = 3). Although cyESC‐derived hematopoietic colony‐forming cells were detected in the newborns (4.1%–4.7%), a teratoma developed in all newborns. The risk of tumor formation was high in this allogeneic transplantation model, given that tumors were hardly observed in immunodeficient mice or fetal sheep that had been xeno‐transplanted with the same cyESC derivatives. It turned out that the cyESC‐derived donor cells included a residual undifferentiated fraction positive for stage‐specific embryonic antigen (SSEA)‐4 (38.2% ± 10.3%) despite the rigorous differentiation culture. When an SSEA‐4‐negative fraction was transplanted (n = 6), the teratoma was no longer observed, whereas the cyESC‐derived hematopoietic engraftment was unperturbed (2.3%–5.0%). SSEA‐4 is therefore a clinically relevant pluripotency marker of primate embryonic stem cells (ESCs). Purging pluripotent cells with this surface marker would be a promising method of producing clinical progenitor cell preparations using human ESCs.