通过比较同种异体小鼠移植模型,研究当前小鼠肿瘤遗传性测试的可推广性。

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cells Translational Medicine Pub Date : 2024-06-14 DOI:10.1093/stcltm/szae019
Takashi Tamura, Tsuyoshi Tahara, Michiko Inoue, Ryota Nanjo, Hirotaka Onoe, Takako Yamamoto, Shin Kawamata
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引用次数: 0

摘要

研究人员对目前通过将人类细胞产品移植到免疫缺陷(NOG)小鼠体内进行的致瘤性测试的可推断性进行了调查。为此,通过肝脏、纹状体或尾静脉移植未分化的人类诱导多能干细胞(hiPSCs)作为阳性对照细胞,评估了 NOG 小鼠形成畸胎瘤的易感性,并评估了 TPD50 值(半数移植小鼠形成畸胎瘤所需的剂量)。然后将其与同种异体小鼠模型的 TPD50 值进行比较。将C57/BL/6(B6)-iPSC或129/Ola(129)-胚胎干细胞(ESC)移植到同种异体小鼠肝脏中的TPD50分别为4.08×105和4.64×104个细胞,而将hiPSC移植到NOG小鼠肝脏中的TPD50为4.64×104个细胞。将 B6-miPSC-能神经细胞、129-mESC-能神经细胞或 129 细胞/B6 异体移植到纹状体的 TPD50 分别为 5.09 × 102、1.0 × 104 和 3.73 × 104 个细胞,而将 hiPSC/NOG 小鼠移植到纹状体的 TPD50 为 1.0 × 103 个细胞。B6-miPSC 或 129-mESC 系统性尾静脉输注的 TPD50 分别为 3.16 × 106 或 5.62 × 106 个细胞,而 1 × 107 B6-miPSCs 在 129 小鼠或 hiPSCs 在 NOG 小鼠输注研究中未观察到发病率。虽然数据集数量有限,但这些数据表明,NOG小鼠经肝脏或纹状体移植未分化的hiPSCs形成畸胎瘤的情况与同种异体小鼠移植模型相当,这表明目前在NOG小鼠中进行的致瘤性试验结果将为推断hPSC衍生产品移植后残留的未分化hPSCs畸胎瘤的发生率提供有用信息。
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Study on the Extrapolability of Current Tumorgenicity Test With Mice by Comparing the Syngeneic or Allogeneic Mouse Transplantation Model.

The extrapolability of the current tumorigenicity test performed by transplanting human cell product into immunodeficient (NOG) mice was investigated. For this purpose, the susceptibility to form teratomas of NOG mice was assessed by transplanting undifferentiated human-induced pluripotent stem cells (hiPSCs) as positive control cells via the liver, striatum, or tail vein and evaluating the TPD50 value (dose required to form teratomas in half of the transplanted mice). This was then compared to the TPD50 of syngeneic or allogeneic mouse models. The TPD50 of C57/BL/6(B6)-iPSC or 129/Ola(129)-embryonic stem cell (ESC) transplanted into the liver of syngeneic mice was 4.08 × 105 and 4.64 × 104 cells, respectively, while the TPD50 of hiPSC administered into the liver of NOG mice was 4.64 × 104 cells. The TPD50 of B6-miPSC-synergic, 129-mESC-synergic, or 129-cell/B6 allogeneic transplantation into the striatum was 5.09 × 102, 1.0 × 104, and 3.73 × 104 cells, respectively, while that of hiPSC/NOG mice was 1.0 × 103 cells. The TPD50 for B6-miPSC or 129-mESC syngeneic tail vein infusion was 3.16 × 106 or 5.62 × 106 cells, respectively, while no incidence was observed from 1 × 107 B6-miPSCs in 129 mice or hiPSCs in NOG mice infusion study. Although the number of data sets was limited, these data indicate that the teratoma formation from transplanted undifferentiated hiPSCs via the liver or striatum in NOG mice is comparable to that in syngeneic or allogeneic mouse transplantation model, suggesting that the result of the current tumorigenicity test in NOG mice would provide useful information to infer the incidence of teratoma from residual undifferentiated hPSCs in hPSC-derived products after transplantation.

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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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