Cells, Vol. 14, Pages 1766: Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats

Cells doi: 10.3390/cells14221766

Authors:
Takayasu Ohtake
Amankeldi A. Salybekov
Tsutomu Sato
Shigeaki Okamura
Masaki Yazawa
Yuki Yano
Mehdi Hassanpour
Mitsuru Yanai
Makoto Imagawa
Takayuki Asahara
Shuzo Kobayashi

To date, no clinical trial has investigated the potential of CD34+ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34+ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34+ cells weekly for three weeks. At eight weeks, the rats’ renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34+ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects.

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Takayasu Ohtake www.mdpi.com