The fate and prospects of stem cell therapy in the treatment of hypoxic–ischemic encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).