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Related Experiment Video

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Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
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Non-Clinical Cell Therapy Development Using the NCG Mouse Model as a Test System.

Viktorija Smutova1, Camila Pará1, Morgan K Foret1

  • 1Charles River Laboratories, Laval, QC, Canada.

International Journal of Toxicology
|January 11, 2023
PubMed
Summary
This summary is machine-generated.

NCG mice support human hematopoietic stem cell engraftment for cell therapy studies. Busulfan preconditioning resulted in higher sustained chimerism, with no observed toxicity in this immunodeficient mouse model.

Keywords:
NCG micecell therapyhematopoietic stem cellshumanized mice

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Area of Science:

  • Immunology
  • Hematology
  • Preclinical Research

Background:

  • NCG mice are triple immunodeficient, lacking T, B, and NK cells, with impaired myeloid function.
  • This model is suitable for evaluating cell therapies due to its immune deficiencies.

Purpose of the Study:

  • To characterize the NCG mouse model for cell therapy assessments.
  • To evaluate toxicity, engraftment, and tumorigenicity of CD34+ human hematopoietic stem progenitor cells (hHSPCs).

Main Methods:

  • NCG mice received sub-lethal irradiation or busulfan myeloablation before intravenous injection of CD34+ hHSPCs.
  • Engraftment was assessed via flow cytometry (hCD45+ cells) and qPCR (human Alu sequences) up to 20 weeks.
  • Tumorigenicity was evaluated using HL-60 cells as a positive control.

Main Results:

  • No significant clinical signs or body weight changes were observed in hHSPC-injected mice.
  • Peripheral blood chimerism of hCD45+ cells reached over 20% by week 10 and remained above 10% at week 17.
  • Busulfan treatment led to higher sustained chimerism compared to irradiation.
  • Human Alu sequences were detected in multiple organs, highest in spleen and bone marrow.
  • Positive control group showed expected mortality due to tumorigenesis.

Conclusions:

  • The NCG mouse model is well-suited for preclinical cell therapy development.
  • Busulfan is an effective myeloablative regimen for achieving robust hHSPC engraftment in NCG mice.
  • The study provides data to inform the design of future cell therapy studies and identify toxicological endpoints.