Ohtake Takayasu, Sato Tsutomu, Tsukiyama Toshitaka, Muraoka Suguru, Mitomo Ayaka, Maruyama Haruka, Yamano Mizuki, Mochida Yasuhiro, Ishioka Kunihiro, Oka Machiko, Moriya Hidekazu, Hidaka Sumi, Masuda Haruchika, Asahara Takayuki, Kobayashi Shuzo
Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan.
Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan.
World J Stem Cells. 2024 Dec 26;16(12):1012-1021. doi: 10.4252/wjsc.v16.i12.1012.
To date, no specific treatment has been established to reverse progressive chronic kidney disease (CKD).
To evaluate the safety and efficacy of autologous CD34 cell transplantation in CKD patients who exhibited a progressive decline in renal function.
The estimated glomerular filtration rate (eGFR) at the beginning of the study was 15.0-28.0 mL/minute/1.73 m. After five days of treatment with the granulocyte colony-stimulating factor, mononuclear cells were harvested and CD34 cells were magnetically collected. CD34 cells were directly injected into the bilateral renal arteries twice (at 0 and 3 months), and their safety and efficacy were evaluated for 6 months.
Four patients were enrolled and completed the study. Three of four patients showed improvement in eGFR slope (eGFR slope > 0 mL/minute/1.73 m), with the monthly slope of eGFR (delta eGFR) changing from -1.36 ± 1.1 (pretreatment) to +0.22 ± 0.71 (at 6 months) mL/minute/1.73 m/month ( = 0.135) after cell therapy. Additionally, intrarenal resistive index ( = 0.004) and shear wave velocity ( = 0.04) were significantly improved after cell therapy. One patient experienced transient fever after cell therapy, and experienced bone pain during granulocyte colony-stimulating factor administration. However, no severe adverse events were reported.
In conclusion, our findings suggest that repetitive peripheral blood-derived autologous CD34 cell transplantation into the renal arteries is safe, feasible, and may be effective for patients with progressive CKD. However, a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34 cells in patients with progressive CKD.
迄今为止，尚未确立可逆转进行性慢性肾脏病（CKD）的特异性治疗方法。
评估自体CD34细胞移植对肾功能呈进行性下降的CKD患者的安全性和疗效。
研究开始时估计肾小球滤过率（eGFR）为15.0 - 28.0 mL/分钟/1.73 m²。在使用粒细胞集落刺激因子治疗5天后，采集单核细胞并通过磁珠法收集CD34细胞。将CD34细胞直接注入双侧肾动脉两次（分别在0个月和3个月），并对其安全性和疗效进行6个月的评估。
4例患者入组并完成研究。4例患者中有3例eGFR斜率改善（eGFR斜率>0 mL/分钟/1.73 m²），细胞治疗后eGFR的月斜率（ΔeGFR）从治疗前的-1.36±1.1变为6个月时的+0.22±0.71 mL/分钟/1.73 m²/月（P = 0.135）。此外，细胞治疗后肾内阻力指数（P = 0.004）和剪切波速度（P = 0.04）显著改善。1例患者在细胞治疗后出现短暂发热，1例在粒细胞集落刺激因子给药期间出现骨痛。然而，未报告严重不良事件。
总之，我们的研究结果表明，将外周血来源的自体CD34细胞重复移植至肾动脉对进行性CKD患者是安全、可行的，且可能有效。然而，有必要进行大规模临床试验以验证使用自体CD34细胞的重复再生细胞治疗对进行性CKD患者的疗效。
