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

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

PMC · DOI: 10.3390/cells14221766 · Cells · 2025-11-11

## TL;DR

Repeated administration of human CD34+ cells reduced kidney damage and improved function in diabetic rats, suggesting potential for treating diabetic nephropathy.

## Contribution

Demonstrates that human CD34+ cells can ameliorate diabetic nephropathy in rats through anti-inflammatory and pro-angiogenic effects.

## Key findings

- CD34+ cell therapy significantly reduced urinary albumin excretion in diabetic rats.
- Cell therapy improved kidney pathology, including mesangial expansion and interstitial fibrosis.
- Transcriptomic analysis showed upregulation of anti-inflammatory and angiogenesis-related genes in treated rats.

## Abstract

What are the main findings?

Human cultured CD34+ cells improved urinary protein excretion and pathological damage in rats with diabetic nephropathy.

Human cultured CD34+ cells upregulated the expression of anti-inflammatory and angiogenesis-related genes in rat kidney tissues.

What are the implications of the main findings?

Human CD34+ cells have a regenerative effect and the potential to improve diabetic nephropathy.

The results of this study support the validity of future clinical trials using CD34+ cells to treat diabetic nephropathy.

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.

## Linked entities

- **Chemicals:** streptozotocin (PubChem CID 29327)
- **Diseases:** diabetic nephropathy (MONDO:0005016)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, Cd34 (CD34 molecule) [NCBI Gene 305081]
- **Diseases:** fibrosis (MESH:D005355), inflammatory (MESH:D007249), Diabetic Nephropathy (MESH:D003928), renal injury (MESH:D007674)
- **Chemicals:** blood glucose (MESH:D001786), creatinine (MESH:D003404), STZ (MESH:D013311)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12651455/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12651455/full.md

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Source: https://tomesphere.com/paper/PMC12651455