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 been recently identified as a novel therapy for HIE. Among the various stem cell sources, ethical hurdles can be avoided using stem cells originating 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 UCB is a rich source of stem and progenitor cells. Many recent manuscripts have shown the treatment effect of UCBCs. Additionally, phase 1 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 actions, such as neurogenesis, angiogenesis, and anti-inflammation, has been suggested in many publications, and most mechanisms are due to growth factors secreted from UCBCs. These diverse actions of UCBC treatment are expected to exert substantial effect for HIE, which has a complex injury mechanism.