Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Feb;41(3):283-300.
doi: 10.1002/pd.5887. Epub 2021 Jan 11.

Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta-analysis

Yada Kunpalin  1   2 , Sindhu Subramaniam  3 , Silvia Perin  3 , Mattia F M Gerli  3   4 , Jan Bosteels  2   5 , Sebastien Ourselin  6 , Jan Deprest  1   2   7 , Paolo De Coppi  2   3 , Anna L David  1   2
Affiliations
Meta-Analysis

Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta-analysis

Yada Kunpalin et al. Prenat Diagn. 2021 Feb.

Abstract

Objective: We performed a systematic review to summarize the efficacy and safety of in utero stem cells application in preclinical models with myelomeningocele (MMC).

Methods: The study was registered with PROSPERO (CRD42019160399). We searched MEDLINE, Embase, Web of Science, Scopus and CENTRAL for publications articles on stem cell therapy in animal fetuses with MMC until May 2020. Publication quality was assessed by the SYRCLE's tool. Meta-analyses were pooled if studies were done in the same animal model providing similar type of stem cell used and outcome measurements. Narrative synthesis was performed for studies that could not be pooled.

Results: Nineteen and seven studies were included in narrative and quantitative syntheses, respectively. Most used mesenchymal stem cells (MSCs) and primarily involved ovine and rodent models. Both intra-amniotic injection of allogeneic amniotic fluid (AF)-MSCs in rat MMC model and the application of human placental (P)-MSCs to the spinal cord during fetal surgery in MMC ovine model did not compromise fetal survival rates at term (rat model, relative risk [RR] 1.03, 95% CI 0.92-1.16; ovine model, RR 0.94, 95% CI 0.78-1.13). A single intra-amniotic injection of allogeneic AF-MSCs into rat MMC model was associated with a higher rate of complete defect coverage compared to saline injection (RR 16.35, 95% CI 3.27-81.79). The incorporation of human P-MSCs as a therapeutic adjunct to fetal surgery in the ovine MMC model significantly improved sheep locomotor rating scale after birth (mean difference 5.18, 95% CI 3.36-6.99).

Conclusions: Stem cell application during prenatal period in preclinical animal models is safe and effective.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of illustrated study selection (adapted from preferred reporting items for systematic reviews and meta‐analysis [PRISMA])
FIGURE 2
FIGURE 2
Risk of bias assessment by SYRCLE's risk of bias tool for animal studies
FIGURE 3
FIGURE 3
Meta‐analysis. (A) Meta‐analysis of fetal rat survival at term after intra‐amniotic injection of allogenic amniotic fluid‐derived mesenchymal stem cells or saline at E17., , , Myelomeningocele (MMC) was created in all studies using retinoic acid. (B) Meta‐analysis of fetal lamb survival at term after application of human second trimester placental (P)‐mesenchymal stem cells (MSCs) during fetal surgical closure of MMC compared to fetal surgical closure alone., , MMC was surgically created in these studies at Gestational Age (GA) 75–77 days; fetal surgical closure was performed 25 days later (GA 100–102 days). (C) Meta‐analysis of defect coverage in the retinoic acid‐induced fetal rat MMC model. Intra‐amniotic injection of allogenic amniotic fluid‐derived mesenchymal stem cells at E17 significantly increased the likelihood of total defect coverage compared to saline injection., , , (D) Meta‐analysis of spinal cord function in the surgical fetal ovine model of MMC determined by sheep locomotor rating scale, after fetal surgery in conjunction with the application of human placental‐derived mesenchymal stem cells compared to fetal surgery alone, , , ,
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Greene ND, Copp AJ. Neural tube defects. Annu Rev Neurosci. 2014;37:221‐242. - PMC - PubMed
    1. Zaganjor I, Sekkarie A, Tsang BL, et al. Describing the prevalence of neural tube defects worldwide: a systematic literature review. PLoS One. 2016;11(4):e0151586. - PMC - PubMed
    1. Syngelaki A, Hammami A, Bower S, Zidere V, Akolekar R, Nicolaides KH. Diagnosis of fetal non‐chromosomal abnormalities on routine ultrasound examination at 11‐13 weeks' gestation. Ultrasound Obstet Gynecol. 2019;54(4):468‐476. - PubMed
    1. Ovaere C, Eggink A, Richter J, et al. Prenatal diagnosis and patient preferences in patients with neural tube defects around the advent of fetal surgery in Belgium and Holland. Fetal Diagn Ther. 2015;37(3):226‐234. - PubMed
    1. Sacco A, Ushakov F, Thompson D, et al. Fetal surgery for open spina bifida. Obstet Gynaecol. 2019;21(4):271‐282. - PMC - PubMed

LinkOut - more resources