Published online Sep 26, 2023. doi: 10.4252/wjsc.v15.i9.931
Peer-review started: May 31, 2023
First decision: June 14, 2023
Revised: June 22, 2023
Accepted: August 23, 2023
Article in press: August 23, 2023
Published online: September 26, 2023
Processing time: 116 Days and 15.6 Hours
Umbilical cord mesenchymal stem cell (MSC) transplantation is a potential therapeutic intervention for atherosclerotic vascular disease. Integrin beta 3 (ITGB3) promotes cell migration in several cell types. However, whether ITGB3-modified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear.
Atherosclerosis is a serious public health problem and more treatment options are needed to explore and identify effective molecules and targets.
The objective of our study was to evaluate the chemotaxis ability of ITGB3-overexpressing MSCs toward inflammatory cells in vitro and plaque tissues in vivo, promoting their therapeutic efficacy in the atherosclerosis mouse model.
Umbilical cord MSCs were isolated and expanded. Lentiviral vectors encoding ITGB3 or green fluorescent protein (GFP) as control were transfected into MSCs. Male apolipoprotein E-/- mice were fed with a high-fat diet (HFD) for 12 wk to induce the formation of atherosclerotic lesions. The HFD-fed mice were randomly separated into three clusters. GFP-labeled MSCs (MSCsGFP) or MSCsITGB3 were transplanted into the mice intravenously via the tail vein. Immunofluorescence staining, Oil red O staining, histological analyses, western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction were used for the analyses. Statistical evaluation between two groups was determined using the unpaired Student’s t-test, and comparisons of more than two groups were performed using a one-way analysis of variance.
MSCsITGB3 successfully differentiated into the “osteocyte” and “adipocyte” phenotypes and were characterized by positive expression (> 91.3%) of CD29, CD73, and CD105 and negative expression (< 1.35%) of CD34 and human leukocyte antigen-DR. MSCsITGB3 showed significantly faster migration than MSCsGFP. ITGB3 overexpression had no effects on MSC viability, differentiation, and secretion. Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites. Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCsITGB3, significantly reducing the plaque area. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSCITGB3 transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro- and anti-inflammatory cytokines.
The study demonstrated that ITGB3 overexpression enhanced the MSC homing ability, providing a potential approach for MSC delivery to plaque sites, thereby optimizing their therapeutic effects.
The ITGB3-modified MSCs can migrate the plaque sites and play an anti-inflammation role, which may be an effective strategy to treat vascular atherosclerotic related diseases.