Complement-dependent control. of teratoma formation by embryonic stem cells
Complement-dependent control. of teratoma formation by embryonic stem cells
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DOI：
10.4049/jimmunol.177.7.4803
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Platt, Jeffrey L.
中科院分区：
文献类型：
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作者：
Koch, Cody A.;Jordan, Corinne E.;Platt, Jeffrey L.
胎儿具有多能干细胞，当转移到成熟个体时可以产生肿瘤。然而，由于尚不清楚的原因，在正常妊娠期间，肿瘤很少在胎儿和/或母亲中形成。我们质疑补体系统是否可以防止多能干细胞形成肿瘤。小鼠胚胎干细胞明显比从这些细胞分化的心肌细胞更容易被异源和同源血清中的补体裂解。用异源血清处理胚胎干细胞，在将残余细胞移植到小鼠体内后，避免了肿瘤的形成。证实了同源补体在防止肿瘤形成中的重要性，未处理的胚胎干细胞在C3缺陷小鼠中比在野生型小鼠中更快地形成肿瘤。胚胎干细胞对补体的敏感性需要一个完整的替代途径，至少部分是由于与分化细胞相比，细胞表面唾液酸相对缺乏。对补体的敏感性和对肿瘤的抵抗力与转移的细胞数量呈负相关。这些发现表明，胚胎干细胞肿瘤的形成部分是由补体的替代途径控制的，并表明对补体的易感性可能代表了多能干细胞的一般特性，可用于预防肿瘤形成。
The fetus has pluripotent stem cells that when transferred to mature individuals can generate tumors. However, for reasons yet unknown, tumors form rarely in the fetus and/or the mother during normal gestation. We questioned whether the complement system might protect against tumor formation by pluripotent stem cells. Murine embryonic stem cells were notably more susceptible than cardiomyocytes differentiated from those cells to lysis by complement in heterologous and homologous sera. Treatment of embryonic stem cells with heterologous serum averted tumor formation after residual cells were transplanted into mice. Confirming the importance of homologous complement in preventing formation of tumors, untreated embryonic stem cells formed tumors more quickly in C3-deficient than in wild-type mice. Susceptibility of embryonic stem cells to complement required an intact alternative pathway and was owed at least in part to a relative deficiency of sialic acid on cell surfaces compared with differentiated cells. Susceptibility to complement and resistance to tumors was inversely related to the number of cells transferred. These findings show that formation of tumors from embryonic stem cells is controlled in part by the alternative pathway of complement and suggest that susceptibility to complement might represent a general property of pluripotent stem cells that can be exploited to prevent tumor formation.