Repetitive administration of cultured human CD34+ cells improve adenine-induced kidney injury in mice

重复施用培养的人类 CD34+ 细胞可改善小鼠腺嘌呤诱发的肾损伤

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作者:Takayasu Ohtake, Shoichi Itaba, Amankeldi A Salybekov, Yin Sheng, Tsutomu Sato, Mitsuru Yanai, Makoto Imagawa, Shigeo Fujii, Hiroki Kumagai, Masamitsu Harata, Takayuki Asahara, Shuzo Kobayashi

Aim

To examine the efficacy of cultured human CD34+ cells with enhanced proliferating potential in kidney injury in mice.

Background

There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease (CKD).

Conclusion

Early intervention using human cultured CD34+ cells significantly improved the progression of tubulointerstitial kidney injury. Repetitive administration of cultured human UCB-CD34+ cells significantly improved tubulointerstitial damage in adenine-induced kidney injury in mice via vasculoprotective and anti-inflammatory effects.

Methods

Human umbilical cord blood (UCB)-derived CD34+ cells were incubated for one week in vasculogenic conditioning medium. Vasculogenic culture significantly increased the number of CD34+ cells and their ability to form endothelial progenitor cell colony-forming units. Adenine-induced tubulointerstitial injury of the kidney was induced in immunodeficient non-obese diabetic/severe combined immunodeficiency 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.

Results

Repetitive administration of cultured UCB-CD34+ cells significantly improved the time-course of kidney dysfunction in the cell therapy group compared with that in the control group. Both interstitial fibrosis and tubular damage were significantly reduced in the cell therapy group compared with those in the control group (P < 0.01). Microvasculature integrity was significantly preserved (P < 0.01) and macrophage infiltration into kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group (P < 0.001).

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