Title:TNF-α Pretreated Hematopoietic Stem Cells Inhibit the Migration and
Inflammatory Response of HUVECs and Attenuate GVHD
Volume: 19
Issue: 5
Author(s): Jilei Sun, Tingting Zhou, Shiyuan Qin, Yaolei Zhang, Yong Yang and Zhitao Wei*
Affiliation:
- Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, No.1478, Gongnong
Road, Changchun, Jilin, 130117, P.R. China
Keywords:
Stem cell transplantation, haematopoiesis, allogeneic transplant, graft-vs-host disease, TNF-α.
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.
