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

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

doi:10.4252/wjsc.v15.i4.268

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

World J Stem Cells. 2023 Apr 26;15(4):268-280. doi: 10.4252/wjsc.v15.i4.268.

Authors

Takayasu Ohtake^{1

2

3}, Shoichi Itaba⁴, Amankeldi A Salybekov⁵, Yin Sheng⁶, Tsutomu Sato⁵, Mitsuru Yanai⁷, Makoto Imagawa⁸, Shigeo Fujii⁴, Hiroki Kumagai⁴, Masamitsu Harata⁹, Takayuki Asahara^{5

10}, Shuzo Kobayashi^{5

11}

Affiliations

¹ Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan.
² Kidney Disease and Transplant center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan.
³ Regenerative Medicine, Shonan Research Institute of Innovative Medicine, Kamakura 247-8533, Kanagawa, Japan. ohtake@shonankamakura.or.jp.
⁴ Kamakura Techno-science Inc., Kamakura 248-0036, Japan.
⁵ Regenerative Medicine, Shonan Research Institute of Innovative Medicine, Kamakura 247-8533, Kanagawa, Japan.
⁶ Advanced Medicine Science, Tokai University School of Medicine, Isehara 259-1193, Japan.
⁷ Department of Pathology, Sapporo Tokushukai Hospital, Sapporo 004-0041, Japan.
⁸ Department of Pathology, Sapporo Medical Center, Sapporo 004-0041, Japan.
⁹ Human Life CORD Japan Inc, Chuo-ku 103-0012, Tokyo, Japan.
¹⁰ Cell Processing and Cell/Genome Analysis Center, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan.
¹¹ Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanazawa, Japan.

Abstract

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

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

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).

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.

Keywords: Adenine; CD34+ cell; Chronic kidney disease; Quality and quantity control culture; Tubulointerstitial injury; Umbilical cord blood.