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Study on the Extrapolability of Current Tumorgenicity Test With Mice by Comparing the Syngeneic or Allogeneic Mouse Transplantation Model.
Tamura, Takashi; Tahara, Tsuyoshi; Inoue, Michiko; Nanjo, Ryota; Onoe, Hirotaka; Yamamoto, Takako; Kawamata, Shin.
Afiliación
  • Tamura T; Department of Science, Technology and Innovation, Kobe University, Japan.
  • Tahara T; Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technology, and RIKEN Center for Biosystems Dynamics Research, Japan.
  • Inoue M; Department of In Vivo Imaging, Advanced Research Promoting Center, Tokushima University, Japan.
  • Nanjo R; Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technology, and RIKEN Center for Biosystems Dynamics Research, Japan.
  • Onoe H; Department of Science, Technology and Innovation, Kobe University, Japan.
  • Yamamoto T; Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technology, and RIKEN Center for Biosystems Dynamics Research, Japan.
  • Kawamata S; Human Brain Research Center, Graduate School of Medicine, Kyoto University, Japan.
Stem Cells Transl Med ; 13(6): 572-581, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38554123
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante Homólogo / Trasplante Isogénico / Células Madre Pluripotentes Inducidas / Ratones Endogámicos C57BL Límite: Animals / Humans Idioma: En Revista: Stem Cells Transl Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante Homólogo / Trasplante Isogénico / Células Madre Pluripotentes Inducidas / Ratones Endogámicos C57BL Límite: Animals / Humans Idioma: En Revista: Stem Cells Transl Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido