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

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.

Amniotic fluid-derived stem cells: potential factories of natural and mimetic strategies for congenital malformations

“…[ 25 ] The stem cell therapy alternative, mainly involving stem cells isolated from gestational tissues, have been reported to improve animal survival and guarantee in utero tissue repair in genetically and mechanically induced spina bifida. [ 11 , 26 – 28 ] Although promising, the inherent risks and hindrances of cell therapy are many and include but are not limited to issues with scalability, cell differentiation abilities and aging, bystander effect which reduces cell potency, number of cells reaching target sites, and therapeutic outcome. [ 29 ]…”

Outcomes of autologous bone marrow mononuclear cell administration in the treatment of neurologic sequelae in children with spina bifida

“…In 2021, Kunpalin et al performed a systematic review and meta‐analysis of 26 published studies using cell administration in utero for spina bifida in animal models. The results from this study revealed that intra‐amniotic injection of allogeneic amniotic fluid mesenchymal stem cells is safe and effective in covering myelomeningocele defects in small animals, while transplantation of human placenta mesenchymal stem cells to the spinal cord of fetal lambs is safe and effective in enhancing lower limb motor function [ 46 ]. All of the above animal studies showed that BM-MNCs/MSCs could repair motor and sensory deficiencies by differentiating into neural lineage cells, secreting growth factors, and proliferating blood vessels.…”

Trends in research related to fetal therapy from 2012 to 2022: a bibliometric analysis

“…Furthermore, in an animal model that is prone to preterm birth and premature rupture of membranes after surgery, transamniotic stem cell therapy enhanced postoperative recovery to a greater extent by promoting local tissue regeneration at the surgical site ( 49 ). The use of biological cells or collagen replacement drugs can also reduce the incidence of complications of inclusion body cysts and myelomeningocele surgery ( 50 ), which has implications for the perfection of myelomeningocele surgery.…”