Meta-Analysis of the Effect of Mesenchymal Stem Cell Transplantation on Vascular Remodeling after Carotid Balloon Injury in Animal Models

Abstract

AimA meta-analysis was conducted to assess the efficacy of mesenchymal stem cell (MSC) transplantation in small animal coronary vessels after balloon injury, to provide data for the design of future pre-clinical experiments and human clinical trials.MethodsThe search strategy included the PubMed, EMBASE, Chinese Biomedical Literature (CBM), and China National Knowledge Infrastructure (CKNI) databases. The endpoint was the ratio of vascular neointima/media (I/M). Moreover, neointimal area, re-endothelialization, and proliferating cell nuclear antigen (PCNA) expression were analyzed. Pooled analyses were conducted using random effects models. Heterogeneity and publication bias were also explored. All data were analyzed using RevMan 5.2 and Stata 12.0.ResultsFifteen studies were reviewed from 238 retrieved animal studies. Compared with controls, MSC transplantation resulted in greater I/M reduction (pooled difference, 0.39; 95% CI, 0.57–0.21; P < 0.0001), greater neointimal area reduction (pooled difference, 0.16; 95% CI, 0.22–0.10; P < 0.0001), decreased PCNA expression (pooled difference, 17.69; 95% CI, 28.94–6.44; P = 0.002), and enhanced re-endothelialization (pooled difference, 3.37; 95% CI, 1.78–4.95; P < 0.0001). The multivariable meta-regression analysis showed that a higher number of transplanted cells (>106; P = 0.017) and later time point of I/M measurement (P = 0.022) were significantly associated with I/M reduction. Subgroup analysis demonstrated a trend for a greater reduction in the ratio of I/M with late MSC transplantation (>1 day), MSCs transplanted through intravenous injection, and atherosclerotic vessels.ConclusionThe meta-analysis results demonstrate that MSC transplantation might improve injured vascular remodeling. In addition to greater efficacy with a greater number of transplanted MSCs (>106), the long-term effect of MSC transplantation appears to be more significant. The findings of this meta-analysis may help to design future, effective MSC trials.

Exosomes from mesenchymal stem cells expressing miR‐125b inhibit neointimal hyperplasia via myosin IE

“…39,[46][47][48] It has been reported that MSC engraftment reduces vascular remodelling after coronary vessel balloon injury, this was demonstrated by a lower I/M, neointimal area and positive expression of PCNA in addition to enhanced re-endothelialisation after MSC transplantation. 46,47 Several studies have reported that exosomes derived from stem cells could target endothelial cells to promote the pro-angiogenic effect after myocardial infarction, and exosomes derived from MSC could target VSMC to promote an antiinflammatory effect. 48 In a rat model of balloon-induced vascular injury, exosomes isolated from EPCs accelerated the process of reendothelialisation in vivo and enhanced endothelial function in vitro.…”

“…Accumulating evidence suggests that exosome‐derived miRNAs may be involved in the regulation of various aspects of neointima formation via the modulation of target cell functions (eg proliferation and migration of VSMCs) and the resulting effects on vasculature homeostasis . It has been reported that MSC engraftment reduces vascular remodelling after coronary vessel balloon injury, this was demonstrated by a lower I/M, neointimal area and positive expression of PCNA in addition to enhanced re‐endothelialisation after MSC transplantation . Several studies have reported that exosomes derived from stem cells could target endothelial cells to promote the pro‐angiogenic effect after myocardial infarction, and exosomes derived from MSC could target VSMC to promote an anti‐inflammatory effect .…”

“…Similarly, extracellular vesicle-derived miR−143 and miR−145 were shown to inhibit the dedifferentiation of VSMCs. 43 Extracellular vesicles derived from adipose MSCs have been shown to limit neointimal hyperplasia and in a study by Liu et al (2015) 44 this was attributed to decreased macrophage infiltration, reduced expression of inflammatory cytokines and downregulation of the MAPK and PI3K signalling pathways. In another study, exosomes derived from pulmonary artery endothelial cells were shown to induce high levels of proliferation and exert anti-apoptotic effects in pulmonary artery smooth muscle cells, contributing to vascular remodelling and the pathogenesis of pulmonary hypertension.…”