Efficacy of mesenchymal stromal cells in the treatment of unexplained recurrent spontaneous abortion in mice: An analytical and systematic review of meta-analyses

PLoS One. 2023 Nov 27;18(11):e0294855. doi: 10.1371/journal.pone.0294855. eCollection 2023.

Abstract

Objectives: Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA.

Methods: A meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis.

Results: A total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], P<0.00001). Moreover, it elicited a positive modulatory impact on the expression profiles of several inflammatory cytokines in the decidual tissue of URSA murine models, inclusive of IL4 (SMD 1.63, 95% CI [0.39, 2.86], P = 0.01), IL10 (SMD 1.60, 95% CI [0.58, 2.61], P = 0.002), IFN-γ (SMD -1.66, 95%CI [-2.79, -0.52], P = 0.004), and TNF-α (SMD -1.98, 95% CI [-2.93, -1.04], P< 0.0001). Subgroup analyses underscored that the administration mode of intraperitoneal and uterine horn injections, and sources of bone MSCs and adipose-derived MSCs contributed positively to the expression of IL4, IL10, and decreased the expression of IFN-γ in decidual tissue of URSA (P<0.05). Conversely, the tail vein injections subgroup was observed with no statistical significance (P>0.05).

Conclusions: The findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation.

Publication types

  • Systematic Review

MeSH terms

  • Abortion, Habitual* / metabolism
  • Abortion, Habitual* / therapy
  • Abortion, Spontaneous*
  • Animals
  • Cytokines
  • Female
  • Humans
  • Interleukin-10
  • Interleukin-4
  • Mesenchymal Stem Cells* / metabolism
  • Meta-Analysis as Topic
  • Mice
  • Pregnancy

Substances

  • Cytokines
  • Interleukin-10
  • Interleukin-4

Grants and funding

This study was funded by the National Natural Science Foundation of China (82305294), the TCM Science and Technology Project of Zhejiang Province (2023ZR038), the Research Project of the Affiliated Hospital of Zhejiang Chinese Medical University (2022FSYYZQ16) and Hangzhou Health Science and Technology Project (A20230675) to ZXX; the National Natural Science Foundation of China (82305299) and the TCM Science and Technology Project of Zhejiang Province (2022ZA120) to MJ; the China Postdoctoral Science Foundation (2023M733193), the TCM Science and the Research Project of Zhejiang Chinese Medical University (2022RCZXZK29) to JYP; the Key project of Zhejiang Provincial Administration of Traditional Chinese Medicine (2022ZZ025) to WSX. None of the authors received a salary from the funders, and all the authors listed have approved the enclosed manuscript.