Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta‐analysis. (11th January 2021)

• Record Type: Journal Article
• Authors: Kunpalin, Yada; Subramaniam, Sindhu; Perin, Silvia; Gerli, Mattia F. M.; Bosteels, Jan; Ourselin, Sebastien; Deprest, Jan; De Coppi, Paolo; David, Anna L.
• Is Part Of: Prenatal diagnosis. Volume 41:Number 3(2021)
• Page Start: 283
• Page End: 300
• Publication Date: 2021-01-11
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5887
• Languages: English
• ISSNs: 0197-3851

Abstract

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. Key Points: What's already known about this topic? Myelomeningocele (MMC) is a severe congenital malformation of the central nervous system causing lifelong sensory and motor impairments, bowel and bladder dysfunctions, and orthopaedic disabilities Fetal surgery for MMC reduces ventriculoperitoneal shunt requirement, increase the ability to walk of the affected children. What does this study add? Safety and efficacy evidence of in utero stem cell application in preclinical MMC settings The application of in utero mesenchymal stem cells is safe and effective in inducing defect coverage and improve motor function in small and large animal models, respectively