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10.3390/cells14221766
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Article

Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats

by
Takayasu Ohtake
1,2,3,*,
Amankeldi A. Salybekov
3,
Tsutomu Sato
3,
Shigeaki Okamura
3,
Masaki Yazawa
3,
Yuki Yano
3,
Mehdi Hassanpour
3,
Mitsuru Yanai
4,
Makoto Imagawa
5,
Takayuki Asahara
3,6 and
Shuzo Kobayashi
2,3
1
Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura 247-8533, Japan
2
Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura 247-8533, Japan
3
Regenerative Medicine, Shonan Research Institute of Innovative Medicine (sRIIM), Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura 247-8533, Japan
4
Department of Pathology, Sapporo Tokushukai Hospital, 1-1-1 Oyaji Higashi, Sapporo 004-0041, Japan
5
Department of Pathology, KKR Sapporo Medical Center, 3-40 Ichijyo Rokuchome, Sapporo 062-0931, Japan
6
Cell Processing and Cell/Genome Analysis Center, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura 247-8533, Japan
*
Author to whom correspondence should be addressed.
Cells 2025, 14(22), 1766; https://doi.org/10.3390/cells14221766
Submission received: 5 October 2025 / Revised: 7 November 2025 / Accepted: 8 November 2025 / Published: 11 November 2025
(This article belongs to the Special Issue Extracellular Vesicles and Cell Therapies in Regenerative Nephrology and Urology)
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Abstract

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.
Keywords: CD34+ cell; diabetic nephropathy; streptozotocin; kidney transcriptomics CD34+ cell; diabetic nephropathy; streptozotocin; kidney transcriptomics

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MDPI and ACS Style

Ohtake, T.; Salybekov, A.A.; Sato, T.; Okamura, S.; Yazawa, M.; Yano, Y.; Hassanpour, M.; Yanai, M.; Imagawa, M.; Asahara, T.; et al. Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats. Cells 2025, 14, 1766. https://doi.org/10.3390/cells14221766

AMA Style

Ohtake T, Salybekov AA, Sato T, Okamura S, Yazawa M, Yano Y, Hassanpour M, Yanai M, Imagawa M, Asahara T, et al. Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats. Cells. 2025; 14(22):1766. https://doi.org/10.3390/cells14221766

Chicago/Turabian Style

Ohtake, Takayasu, Amankeldi A. Salybekov, Tsutomu Sato, Shigeaki Okamura, Masaki Yazawa, Yuki Yano, Mehdi Hassanpour, Mitsuru Yanai, Makoto Imagawa, Takayuki Asahara, and et al. 2025. "Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats" Cells 14, no. 22: 1766. https://doi.org/10.3390/cells14221766

APA Style

Ohtake, T., Salybekov, A. A., Sato, T., Okamura, S., Yazawa, M., Yano, Y., Hassanpour, M., Yanai, M., Imagawa, M., Asahara, T., & Kobayashi, S. (2025). Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats. Cells, 14(22), 1766. https://doi.org/10.3390/cells14221766

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