Umbilical Cord Blood Cell Therapy in Neonatal Hypoxic-Ischemic Brain Injury

Hypoxic-ischemic brain injury in perinatal period, especially in preterm infants, causes neurological impairment including cerebral palsy (CP). The numerouscomplex mechanisms are involved in brain injury in preterm infants. Hypotension, hypoxia-ischemia and inflammation cause mitochondrial dysfunction, activation ofapoptosis, excitotoxicity, oxidative stress and other inflammatory pathways. These events disrupt the normal differentiation, decrease neurotrophic factors and synapticinput from adjacent cells that result in white matter insult in the developing brain and can lead to spastic CP.Currently, stem cell therapy is suggested as the gold standard for the treatment of CP due to ability of stem cells to differentiate into several cell types and promote tissue repair. Generally, stem cells are classified into three categories regarding their source including embryonic stem cells (ESCs), fetal-derived stem cells, and adult stem cells. ESCs are pluripotential and can generate all three germ layer cells. However, they can also be tumorigenic and their transplantation has safety concerns. Moreover, their isolation from embryos, have ethical issues. Adult stem cells are obtained from a few sources such as bone marrow, adipose tissue, dental pulp, and neural progenitor cells in the subventricular region of the brain. Fetal-derived stem cells are isolated from placental tissue and umbilical cord blood and consisted of hematopoietic stem cells, mesenchymal stromal cells, endothelial progenitor cells, and immunosuppressive cells such as monocyte-derived suppressor cells and regulatory T cells. They have greater differentiation ability than adult stem cells and can be easily collected from placenta discarded at birth routinely. They have also, low immunogenicity and low risk of rejection or graft versus host reaction. UCB is readily available in nonexpensive and large quantities and is feasible to obtain a source of stem cells that its collection has no ethical issues. Treatment with UCB cells in neonates during the first few days after brain injury was demonstrated excellent results in neuroprotection or neurodegeneration. These effects were expressed by the secretion of many trophic cytokines, angiogenic and neurotrophic growth factors. After engraftment, these cells release factors with direct effect on stimulation and expansion of neural stem cells. They have also antiinflammatory, anti-apoptotic, antioxidant and immunomodulatory effects and protect neurons, astrocytes, and oligodendrocytes. Oligodendrocytes are responsible for myelin synthesis and their damage leads to hypomyelination and white matter insult after brain injury. UCB cell given early in hypoxic-ischemic brain insult, improve pathology by decreasing apoptosis and microglial activation. Biochemical profile in brain also restores in normal situation as detected by magnetic resonance spectroscopy for lactate: N-acetyl aspartate ratio. UCB cell therapy has been presented as a promising clinical treatment for the hypoxic injury of the brain in neonates. However, further studies are needed to explain about the optimal dose, best time of administration, cell type, rout of injection, and targeted therapy in infants and children.

کلیدواژه ها:

Cord blood cell therapy ، Cerebral palsy ، Neonatal hypoxic brain injury