Diverse actions of cord blood cell therapy for hypoxic‐ischemic encephalopathy

Perinatal hypoxic‐ischemic encephalopathy (HIE) is a major cause of neonatal death and permanent neurological deficits. However, effective treatments have not yet been established, except therapeutic hypothermia, which is not effective for severe HIE; therefore, developing a novel therapy for HIE is of the utmost importance. Stem cell therapy has recently been identified as a novel therapy for HIE. Among the various stem cell sources, ethical hurdles can be avoided by using stem cells that originate from non‐embryonic or non‐neural tissues, such as umbilical cord blood cells (UCBCs), which are readily available and can be exploited for autologous transplantations. Human UCBs are a rich source of stem and progenitor cells. Many recent studies have reported the treatment effect of UCBCs. Additionally, phase I clinical trials have already been conducted, showing this therapy’s safety and feasibility. One advantage of stem cell therapies, including UCBC administration, is that they exert treatment effects through multifaceted mechanisms. According to the findings of several publications, replacement of lost cells, namely, engraftment and differentiation into neuronal cells, is not likely to be the main mechanism. However, the association between UCBCs and various mechanism of action, such as neurogenesis, angiogenesis, and anti‐inflammation, has been suggested in many studies, and most mechanisms are due to growth factors secreted from UCBCs. These diverse actions of UCBC treatment are expected to exert a substantial effect on HIE, which has a complex injury mechanism.