Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies.

Inês Serrenho,Graça Baltazar,Carla M Cardoso,Miguel Rosado,Alexandra Dinis,Bruno Manadas,Mário Grãos

doi:10.3390/ijms22063142

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in the perinatal period. This condition results from a period of ischemia and hypoxia to the brain of neonates, leading to several disorders that profoundly affect the daily life of patients and their families. Currently, therapeutic hypothermia (TH) is the standard of care in developing countries; however, TH is not always effective, especially in severe cases of HIE. Addressing this concern, several preclinical studies assessed the potential of stem cell therapy (SCT) for HIE. With this systematic review, we gathered information included in 58 preclinical studies from the last decade, focusing on the ones using stem cells isolated from the umbilical cord blood, umbilical cord tissue, placenta, and bone marrow. Outstandingly, about 80% of these studies reported a significant improvement of cognitive and/or sensorimotor function, as well as decreased brain damage. These results show the potential of SCT for HIE and the possibility of this therapy, in combination with TH, becoming the next therapeutic approach for HIE. Nonetheless, few preclinical studies assessed the combination of TH and SCT for HIE, and the existent studies show some contradictory results, revealing the need to further explore this line of research.

Highlights

Hypoxic-ischemic encephalopathy (HIE) is one of the major causes of neonatal death and long-term disability, leading to chronic motor and cognitive impairments [1]
therapeutic hypothermia (TH) is the current standard of care for HIE in term neonates in developing countries, it is not entirely effective in preventing mortality or neurodevelopmental disabilities in HIE patients, especially those diagnosed with severe HIE [6]
Analysis and Discussion From the 58 studies included in this systematic review (Supplementary Table S1), we identified 83 different protocols for stem cell therapy in animal models for HIE (Supplementary Table S2)

Summary

Introduction

Hypoxic-ischemic encephalopathy (HIE) is one of the major causes of neonatal death and long-term disability, leading to chronic motor and cognitive impairments [1]. The different outcomes of this condition can be severe, profoundly affecting the daily life of patients and their families. This condition represents a major economic burden to the government and caretakers [3]. The estimated incidence of HIE is variable across studies, ranging from 1 to 8 cases per 1000 live births [5]. Neonatal HIE incidence is approximately 0.5 to 1 case per 1000 live births [6]; the global estimate is highly influenced by the higher incidence found in developing countries [7]. Infants diagnosed with HIE have a reserved prognosis since the HIE mortality rate is about 25%, and 20% of the survivors develop moderate to severe long-term impairment [7]

Methods

Findings

Discussion

Conclusion