Meta-analysis of the effect of mesenchymal stem cell transplantation on vascular remodeling after carotid balloon injury in animal models

PLoS One. 2015 Mar 26;10(3):e0120082. doi: 10.1371/journal.pone.0120082. eCollection 2015.

Abstract

Aim: A 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.

Methods: The 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.

Results: Fifteen 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.

Conclusion: The 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery Injuries / etiology*
  • Carotid Artery Injuries / therapy*
  • Disease Models, Animal
  • Mesenchymal Stem Cell Transplantation*
  • Mice
  • Rabbits
  • Treatment Outcome
  • Vascular Remodeling*

Grants and funding

The work was supported by National Natural Science Foundation of China (No. 81160018, 81460059), The Corps Doctor Foundation (No. 2014BB018), Shihezi University Outstanding Youth Science and Technology Talent Cultivation Plan (2013ZRKXJQ05), and One Thousand Youth Talents Plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.