Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Most clinical studies fail in spite of promising mouse studies, in part due to fundamental differences between mice and human responses. Attempts have been made to generate humanized mouse models that mimic human responses more closely. However, there is little information on human immune cell composition of humanized mouse kidney and how it compares 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 irradiated (100 cGy) and 1×105 human cord blood derived CD34+ hematopoietic stem cells transferred intravenously. Kidneys were harvested from perfused humanized NOG (huNOG) and huNOGEXL mice, 20 weeks post engraftment. Normal human kidney samples were collected from visibly unaffected portion of nephrectomies for 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 humanized mouse strains 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.
*Conclusions: These data demonstrate that humanized mice kidneys have significant numbers of human immune cells. Furthermore, immune cell composition of humanized mice kidney has key similarities and differences compared to human kidney. Humanized mice can be useful to study kidney diseases. However, it is important to know key strengths and limitations of this approach.
To cite this abstract in AMA style:Noel S, Kurzhagen JT, Lee S, Sadasivam M, Hamad AR, Pierorazio PM, Rabb H. Immune Cells Composition of Humanized Mouse Kidney Compared to Normal Human Kidney [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/immune-cells-composition-of-humanized-mouse-kidney-compared-to-normal-human-kidney/. Accessed December 15, 2019.
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