TNF-α Pretreated Hematopoietic Stem Cells Inhibit the Migration and Inflammatory Response of HUVECs and Attenuate GVHD.

IF 2.1 4区医学 Q4 CELL & TISSUE ENGINEERING

Current stem cell research & therapy Pub Date : 2024-01-01 DOI:10.2174/1574888X18666230731150317

Jilei Sun, Tingting Zhou, Shiyuan Qin, Yaolei Zhang, Yong Yang, Zhitao Wei

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Abstract

Background: Hematologic diseases have seriously threatened human health. Although hematopoietic stem cell transplantation (HSCT) is an effective curative option, the complications, especially graft-versus-host disease (GVHD), are a big problem.

Methods: TNF-α pretreatment of hematopoietic stem cells. Apoptosis was detected by flow cytometry, Transwell, and wound healing assays were used to assess cell migration and invasion, E-selectin expression was observed by fluorescence imaging, the levels of NO were measured by a kit, the expression of Ecadherin, MMP2, and MMP9 was detected in cells by qRT-PCR, and western blot was used to analyze the expression of E-cadherin, CXCL12, MCP-1, MCP-3, MMP2, and MMP9.

Results: TNF-α induces a high apoptosis rate of CD3, CD19, and CD133 and a low apoptosis rate of CD34. The level of Fas and TNF-R1 was significantly high than that of TNF-R2. HSCs treated with TNF- α declined the invasion and migration of HUVECs. E-selectin, MMP2 and MMP9 mRNA levels of HUVECs and MMP2, CXCL12, MCP-1, and MCP-3 were decreased after HSCs-TNF-α treatment, while the E-cadherin mRNA and protein level of HUVECs was enhanced with HSCs-TNF-α treatment.

Conclusion: TNF-α pretreated HSCs can lead to reduced levels of migration, adhesion, and chemokines of HUVECs, thereby declining the inflammatory response and GVHD.

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TNF-α 预处理造血干细胞可抑制 HUVECs 的迁移和炎症反应并减轻 GVHD。

背景：血液病严重威胁人类健康。虽然造血干细胞移植（HSCT）是一种有效的治疗方法，但其并发症，尤其是移植物抗宿主疾病（GVHD），也是一个大问题：方法：TNF-α预处理造血干细胞。方法：TNF-α预处理造血干细胞，流式细胞术检测细胞凋亡，Transwell和伤口愈合试验评估细胞迁移和侵袭，荧光成像观察E-选择素表达，试剂盒检测NO水平，qRT-PCR检测细胞中Ecadherin、MMP2和MMP9的表达，Western印迹分析E-cadherin、CXCL12、MCP-1、MCP-3、MMP2和MMP9的表达：结果：TNF-α能诱导CD3、CD19和CD133的高凋亡率和CD34的低凋亡率。Fas和TNF-R1的水平明显高于TNF-R2。经 TNF- α 处理的造血干细胞可降低 HUVEC 的侵袭和迁移。HSCs-TNF-α处理后，HUVECs的E-选择素、MMP2和MMP9 mRNA水平以及MMP2、CXCL12、MCP-1和MCP-3水平均下降，而HSCs-TNF-α处理后，HUVECs的E-cadherin mRNA和蛋白水平均升高：结论：TNF-α预处理的造血干细胞可降低HUVECs的迁移、粘附和趋化因子水平，从而减轻炎症反应和GVHD。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current stem cell research & therapy CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

4.20

自引率

3.70%

发文量

197

审稿时长

>12 weeks

期刊介绍： Current Stem Cell Research & Therapy publishes high quality frontier reviews, drug clinical trial studies and guest edited issues on all aspects of basic research on stem cells and their uses in clinical therapy. The journal is essential reading for all researchers and clinicians involved in stem cells research.