Variation in the Incidence of Teratomas After the Transplantation of Nonhuman Primate ES Cells Into Immunodeficient Mice
Variation in the Incidence of Teratomas After the Transplantation of Nonhuman Primate ES Cells Into Immunodeficient Mice
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DOI：
10.3727/096368908786991560
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Hanazono, Yutaka
中科院分区：
文献类型：
--
作者：
Kishi, Yukiko;Tanaka, Yujiro;Hanazono, Yutaka
胚胎干细胞(ES)移植到免疫缺陷小鼠体内可产生畸胎瘤，但影响传代的条件仍有待阐明。将非人灵长类食蟹猴ES细胞在不同条件下移植到免疫缺陷小鼠体内，移植细胞的数量、物理状态(成团或单个分离细胞)、移植部位、分化状态和免疫状态均有所不同。然后评估其致瘤性。将食蟹猴ES细胞成团移植到非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)或NOD/SCID/Gamma c(NULL)(NOG)小鼠的下肢肌肉中，移植1×10(5)或更多细胞的小鼠均出现畸胎瘤，而移植1×10(3)细胞的小鼠未见畸形瘤形成。然而，当这些细胞被作为分离细胞移植时，所有小鼠形成畸胎所需的细胞数量增加到5x10(5)。当注射丛状细胞时。皮下(而不是肌肉内)，这个数字也增加到5x10(5)。当食蟹猴ES细胞来源的祖细胞(1×10(6))，包括剩余的多能细胞，被移植到NOG或NOD/SCID小鼠的下肢肌肉中，畸胎瘤的发生率在不同品系之间存在差异；5只NOG小鼠中有5只发生了畸胎瘤，但在5只NOD/SCID小鼠中只有2只发生了畸胎瘤。畸胎瘤的发生率根据移植细胞和受体小鼠的不同而有很大差异。因此，必须对致瘤性给予相当大的关注。
Embryonic stem (ES) cells have the ability to generate teratomas when transplanted into immunodeficient mice, but conditions affecting the generation remain to be elucidated. Nonhuman primate cynomolgus ES cells were transplanted into immunodeficient mice under different conditions; the number of transplanted cells, physical state (clumps or single dissociated cells), transplant site, differentiation state, and immunological state of recipient mice were all varied. The tumorigenicity was then evaluated. When cynomolgus ES cells were transplanted as clumps into the lower limb muscle in either nonobese diabetic/severe combined immunodeficiency (NOD/SCID) or NOD/SCID/gamma c(null) (NOG) mice, teratomas developed in all the animals transplanted with 1 x 10(5) or more cells, but were not observed in any mouse transplanted with 1 x 10(3) cells. However, when the cells were transplanted as dissociated cells, the number of cells necessary for teratornas to form in all mice increased to 5 x 10(5). When the clump cells were injected. subcutaneously (instead of intramuscularly), the number also increased to 5 x 10(5). When cynomolgus ES cell-derived progenitor cells (1 x 10(6)), which included residual pluripotent cells, were transplanted into the lower limb muscle of NOG or NOD/SCID mice, the incidence of teratomas differed between the strains; teratomas developed in five of five NOG mice but in only two of five NOD/SCID mice. The incidence of teratomas varied substantially depending on the transplanted cells and recipient mice. Thus, considerable care must be taken as to tumorigenicity.