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自体脂肪来源间充质干细胞治疗腹膜纤维化的潜力:一项初步研究。

Potential of Autologous Adipose-Derived Mesenchymal Stem Cells in Peritoneal Fibrosis: A Pilot Study.

机构信息

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Arch Iran Med. 2023 Feb 1;26(2):100-109. doi: 10.34172/aim.2023.16.

Abstract

BACKGROUND

We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients.

METHODS

We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2±0.1×10 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNI-PET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor α (TNF-α), , IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-β), smooth muscle actin (𝛼-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24.

RESULTS

Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration - small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-β, α-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study.

CONCLUSION

Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies.

摘要

背景

我们旨在确定自体脂肪组织来源间充质干细胞(AD-MSCs)全身治疗对腹膜透析(PD)患者不同腹膜功能和炎症参数的影响。

方法

我们纳入了 9 例超滤失败(UFF)的 PD 患者。患者经肘静脉输注 1.2±0.1×10 细胞/kg 的 AD-MSCs,在输注后 3、6、12、16 和 24 周的时间点进行随访。在基线和 12 周及 24 周时进行 UNI-PET 评估腹膜特性。在基线和 3、6、12、16 和 24 周时,通过酶联免疫吸附试验(ELISA)测量系统和腹膜中肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)和 CA125 的水平,通过定量实时 PCR 测量 PD 流出细胞中转化生长因子-β(TGF-β)、平滑肌肌动蛋白(𝛼-SMA)和纤维母细胞特异性蛋白-1(FSP-1)的基因表达水平。

结果

UF 容量指数有轻微改善:自由水转运(FWT,32%)、超滤-小孔隙(UFSP,18%)、总超滤(UFT,25%)、葡萄糖渗透系数(OCG,25%)、D/P 肌酐(从 0.75 升至 0.70)和 Dt/D0 葡萄糖(从 0.23 升至 0.26)。系统和腹膜 CA125 水平略有升高,TGF-β、α-SMA 和 FSP-1 的基因表达水平略有下降,在第 12 周更为明显,研究结束时消失。

结论

我们的研究结果首次表明 MSC 治疗临床研究中腹膜损伤的潜力。我们的结果可以被视为假设提示,需要在未来的研究中得到证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd37/10685899/7c9827b2775c/aim-26-100-g001.jpg

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