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.
Highlights
Percutaneous coronary intervention (PCI) is an effective treatment method for coronary heart disease
mesenchymal stem cell (MSC) transplantation resulted in greater I/M reduction, greater neointimal area reduction, decreased proliferating cell nuclear antigen (PCNA) expression, and enhanced re-endothelialization
The meta-analysis results demonstrate that MSC transplantation might improve injured vascular remodeling
Summary
Percutaneous coronary intervention (PCI) is an effective treatment method for coronary heart disease. Post-angioplasty restenosis is caused largely by smooth muscle cell proliferation and neointimal proliferation, as well as elastic recoil [1]. A number of studies have suggested that inward vascular neointimal remodeling is the main cause of restenosis [2]. Despite an increase in the number of animal experiments studying the effects of MSCs on the repair of vascular injury, there is variation in experimental design and the results. Animal experiments provide relevant information for clinical practice, while pre-clinical studies have to anticipate if the new therapy is feasible and effective. There are still a number of unknowns regarding MSC therapy in clinical practice, including the effect of MSCs on vascular remodeling after carotid balloon injury, effective number of MSCs, appropriate route, and appropriate timing of cell delivery
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