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原发性胆汁性胆管炎患者经培养和自体输注后骨髓和外周血单个核细胞表型的变化。

Bone Marrow and Peripheral Blood Mononuclear Cell Phenotype Changes after Cultivation and Autologous Infusion in Patients with Primary Biliary Cholangitis.

机构信息

Cell Technologies, Transplantation and Research Department, National Scientific Medical Center, Astana, Kazakhstan.

PerciaVista R&D Co. Shiraz, Iran.

出版信息

Iran J Med Sci. 2024 Sep 1;49(9):559-572. doi: 10.30476/ijms.2023.99613.3172. eCollection 2024 Sep.

Abstract

BACKGROUND

Primary biliary cholangitis (PBC) is a condition affecting the liver and immune system. In this study, the impact of autologous bone marrow-derived mononuclear cell (BM-MNC) transplantation on PBC patients was investigated.

METHODS

Sixteen eligible PBC patients participated at the National Scientific Medical Center in Astana, Kazakhstan, between 2017 and 2022, and BM-MNCs were harvested from their anterior iliac crest. After isolating and cultivating the BM-MNCs, they were infused back into the patient's peripheral veins. Changes in BM-MNC and peripheral blood mononuclear cell (PB-MNC) phenotypes were assessed before and after a 24-hour cultivation period and 72 hours post-transplantation. We monitored liver function parameters over 6-month intervals and conducted flow cytometry analysis to assess CD markers on BM-MNCs before and after cultivation and PB-MNCs before and after transplantation. Statistical analysis included the Friedman test for liver parameters and the Wilcoxon signed-rank test for BM-MNC and PB-MNC comparisons.

RESULTS

Our findings revealed significant reductions in liver function tests after multiple transplantations. Flow cytometry analysis before and after a 24-hour culture and autologous BM-MNC infusion revealed the expansion of specific cell populations, with significant increases in CD3+, CD4+, CD16+, CD20+, CD25+, CD34+, CD105+, CD73+, СD117+, and CD34+populations, while CD4+25+, CD34+105+, and CD4+FOXP3+ populations decreased. Interestingly, a contradictory finding was observed with a decrease in bone marrow CD34+105+ cell lines (P=0.03) alongside an increase in peripheral CD34+105+ population (P=0.03).

CONCLUSION

In summary, our study shows that BM-MNC transplantation in PBC patients leads to changes in immune cell populations and liver function. These findings suggest potential therapeutic applications of BM-MNC transplantation in managing PBC and offer insights into the dynamics of immune cells associated with this treatment approach.

摘要

背景

原发性胆汁性胆管炎(PBC)是一种影响肝脏和免疫系统的疾病。本研究旨在探讨自体骨髓源性单核细胞(BM-MNC)移植对 PBC 患者的影响。

方法

2017 年至 2022 年期间,哈萨克斯坦阿斯塔纳国家科学医学中心的 16 名符合条件的 PBC 患者参与了该研究,并从其前髂嵴采集 BM-MNC。分离和培养 BM-MNC 后,将其输注回患者的外周静脉。在 24 小时培养期和移植后 72 小时前后评估 BM-MNC 和外周血单核细胞(PB-MNC)表型的变化。我们在 6 个月的时间间隔内监测肝功能参数,并进行流式细胞术分析,以评估培养前后 BM-MNC 和移植前后 PB-MNC 的 CD 标志物。统计分析包括 Friedman 检验用于肝功能参数,Wilcoxon 符号秩检验用于 BM-MNC 和 PB-MNC 的比较。

结果

我们的研究结果表明,多次移植后肝功能检查显著降低。24 小时培养和自体 BM-MNC 输注前后的流式细胞术分析显示,特定细胞群的扩增,CD3+、CD4+、CD16+、CD20+、CD25+、CD34+、CD105+、CD73+、СD117+和 CD34+细胞群显著增加,而 CD4+25+、CD34+105+和 CD4+FOXP3+细胞群减少。有趣的是,观察到与骨髓 CD34+105+细胞系减少(P=0.03)相反的是,外周 CD34+105+群体增加(P=0.03)。

结论

综上所述,我们的研究表明,BM-MNC 移植可导致 PBC 患者免疫细胞群和肝功能的变化。这些发现表明,BM-MNC 移植在治疗 PBC 方面具有潜在的治疗应用,并为这种治疗方法相关的免疫细胞动力学提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/529f/11452589/2d3a1090f847/IJMS-49-559-g001.jpg

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