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Kidney Week

Abstract: TH-PO078

Immunophenotypic Analysis of Humanized Mouse Kidney in Comparison with Human Kidney

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Noel, Sanjeev, Johns Hopkins University, Baltimore, Maryland, United States
  • Kurzhagen, Johanna T., Johns Hopkins University, Baltimore, Maryland, United States
  • Lee, Sul A, Johns Hopkins University, Baltimore, Maryland, United States
  • Sadasivam, Mohanraj, Johns Hopkins University, Baltimore, Maryland, United States
  • Hamad, Abdel, Johns Hopkins University, Baltimore, Maryland, United States
  • Pierorazio, Phillip M., Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Rabb, Hamid, Johns Hopkins University, Baltimore, Maryland, United States
Background

Most positive intervention studies in mice fail in human trials, in part due to fundamental differences between mice and humans. Humanizing mouse tissue aims to bring the mouse experimental model closer to human responses. Given the strong data supporting immune cells in acute kidney injury pathogenesis and repair, it is important to test relevance to humans. However, there is little information on immune phenotype of humanized mouse kidney in comparison to normal human kidney. We evaluated immune cell composition in the kidneys of two humanized mice strains and compared it to that of normal human kidney tissue.

Methods

For humanization, 4 week old NOG and NOGEXL female mice were irradiate (100 cGy) and 1x105 human cord blood derived CD34+ hematopoietic stem cells transferred intravenously. Kidneys were harvested from well perfused humanized NOG (huNOG) and huNOGEXL mice, 20 weeks post engraftment. Normal human kidney samples were collected from visibly unaffected portion of nephrectomies from renal cell carcinoma. Kidney mononuclear cells isolated from mouse and human kidneys were analyzed for human CD45, TCR, CD4, CD8, CD20, CD16, CD14, CD11c and CD206 using flow cytometry. n=3/group each humanized mouse strain and human kidney.

Results

The frequency (mean%±SEM) of human CD45+ cells was higher (p=0.04) in huNOG (12.5±2.9) mouse kidney compared to normal human kidney (6.4±1.3). Similarly, the frequency of CD11c+ cells was higher (p=0.02) in huNOG (28.0±4.1) kidney compared to normal human kidney (17.8±1.4). The frequency of CD16+ cells was significantly reduced in both huNOG (7.6±5.5, p=0.03) and huNOGEXL (4.9±1.0, p=0.01) kidney compared to human kidney (31.5±6.3). CD8 T cell frequency was significantly lower (p=0.03) in huNOGEXL (17.2±2.6) compared to human kidney (34.8±4.4). There was no statistically significant difference in the frequency of TCR+, CD4+, CD20+, CD14+ and CD206+ cells between humanized mice kidney and human kidney.

Conclusion

These data demonstrate that huNOG and huNOGEXL kidneys have significant numbers of human immune cells. Furthermore, there are key similarities and differences between different background strains compared to human kidney. Humanizing mice to study kidney disease is a useful approach however it is important to know key strengths and limitations of this approach.

Funding

  • NIDDK Support