Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2023; 15(9): 931-946
Published online Sep 26, 2023. doi: 10.4252/wjsc.v15.i9.931
Integrin beta 3-overexpressing mesenchymal stromal cells display enhanced homing and can reduce atherosclerotic plaque
Hai-Juan Hu, Xue-Ru Xiao, Tong Li, De-Min Liu, Xue Geng, Mei Han, Wei Cui
Hai-Juan Hu, Tong Li, De-Min Liu, Xue Geng, Wei Cui, First Division, Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease of Hebei Province, Shijiazhuang 050000, Hebei Province, China
Xue-Ru Xiao, Department of Obstetrics, Shijiazhuang People's Hospital, Shijiazhuang 050030, Hebei Province, China
Mei Han, Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Author contributions: Cui W and Han M designed and coordinated the study; Hu HJ, Xiao XR, Li T, Liu DM and Geng X performed the experiments and acquired and analyzed data; Cui W interpreted the data; Hu HJ and Liu DM wrote the manuscript; all authors revised the manuscript and approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 82100301; and Key Science and Technology Research Program of Hebei Provincial Department of Health, No, 20221014.
Institutional review board statement: The study was reviewed and approved by the Ethical Committee of the Second Hospital of Hebei Medical University, No. 2021-R496.
Institutional animal care and use committee statement: Laboratory Animal Use and Management Committee has been carefully discussed and voted on May 27, 2021 for the subject animal-related content, 10 voters, 10 people suggested a formal experiment, and made the following recommendations. The design is reasonable, in line with the animal requirements. The ethics committee agreed to carry out a formal experiment.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Wei Cui, PhD, Professor, First Division, Department of Cardiology, The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease of Hebei Province, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China.
Received: May 31, 2023
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
Research background

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.

Research motivation

Atherosclerosis is a serious public health problem and more treatment options are needed to explore and identify effective molecules and targets.

Research objectives

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.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.