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Abstract: SA-PO346

Repetitive Administration of Cultured Human CD34+ Cells Improve Adenine-Induced Kidney Injury in Mice

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Ohtake, Takayasu, Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
  • Salybekov, Amankeldi, Regenerative Medicine, Shonan Research Institute of Innovative Medicine (sRIIM), Kamakura, Kanagawa, Japan
  • Asahara, Takayuki, Regenerative Medicine, Shonan Research Institute of Innovative Medicine (sRIIM), Kamakura, Kanagawa, Japan
  • Kobayashi, Shuzo, Regenerative Medicine, Shonan Research Institute of Innovative Medicine (sRIIM), Kamakura, Kanagawa, Japan
Background

There is no established treatment to impede the progression of diabetic kidney disease in human.

Methods

We evaluated the efficacy of cultured human CD34+ cells with enhanced proliferating potential in chronic kidney injury model in mice. Human umbilical cord blood (UCB)-derived CD34+ cells were incubated for one week in vasculogenic conditioning medium. This culture method significantly increased the number of CD34+ cells (60-fold) and their ability to form endothelial progenitor cell colony-forming units (40-fold). Adenine-induced tubulointerstitial chronic kidney injury was induced in NOD/SCID mice, and cultured human UCB-CD34+ cells were administered at a dose of 1 × 106/mouse on days 7, 14, and 21 after the start of adenine diet (cell therapy group n=18). In the control group (n=17), vehicle was administered at the same time point. Time-course of kidney function, pathological damage, and CD31-positive peritubular capillary density and macrophage infiltration in the kidney at the time of sacrifice (day 28) were evaluated.

Results

Repetitive administration of cultured UCB-CD34+ cells significantly improved the time-course of serum creatinine levels in the cell therapy group compared with that in the control group (1.09 ± 0.09 mg/dL vs 1.41 ± 0.14 mg/dL on day 28, p =0.035). Both interstitial fibrosis area and tubular injury score were significantly reduced in the cell therapy group compared with that in the control group (interstitial fibrosis: 8.1 ± 5.4% vs 16.3 ± 7.0%, p < 0.01, tubular injury score: 1.48 ± 1.27 vs 2.83 ± 1.00, p < 0.01). Peritubular capillary density was significantly preserved in the cell therapy group compared with that in the control group (57.3 ± 6.4% vs 31.0 ± 6.1%, p < 0.01), and macrophage infiltration in the kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group (1.3 ± 0.3% vs 14.4 ± 1.1%, p < 0.001).

Conclusion

Repetitive administration of cultured human UCB-CD34+ cells significantly improved kidney dysfunction and chronic tubulointerstitial damage in adenine-induced kidney injury in mice via the protective effect of microvasculature integrity and anti-inflammatory effects. A clinical trial using cultured human UCB-CD34+ cells for progressive kidney disease might be expected.