Stem cells for brain repair in neonatal hypoxia–ischemia

Abstract

Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats

“…This is described as fibrillar reactive astrocytosis and is associated with hyperplasia and hypertrophy of astrocytes. The reactive astrocytes form the glial scar that accumulates around the lesion forming a physical barrier and an inhibitory environment for axonal regeneration and remyelination (COUTTS; KEIRSTEAD, 2008). The significant reduction of the reactivity of astrocytes in the treated animals observed in this study suggests that MSC may have reduced the response of astrocytes and consequently may act by reducing the inhibitory effects of scar tissue providing a more permissive environment for axonal extension.…”

“…Hence, when administered intravenously, MSC act beyond increasing the expression of neurotrophic growth factors post injury (MAHMOOD et al, 2004), since they actually participate as bimodal cells, by providing immunomodulatory activity (CHICHA et al, 2013).…”

Application of mesenchymal stem cells in paediatrics

“…Their aim is to ascertain whether MSC therapy is effective in the treatment of brain leukodystrophy in children aged 4 and over, autism in children between 3 and 12 years of age, damage to the spinal cord in children over 2, congenital ataxia, hypoxic ischemic encephalopathy, haemorrhage IV degree, encephalopathy associated with ischemia and hypoxia of the brain, as well as cerebral palsy [1,9,46]. From 2016 on, MSC therapy has been utilized in treating the autosomal recessive disease of motor neuron and Spinal Muscular Atrophy.…”

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

“…The cascade of biochemical and physiological events that occur during and acutely following a stroke event occurs rapidly and with implications for tissue viability and ultimately outcome 2 . Cerebral hypoxia-ischemia (H-I), which leads to hypoxic-ischemic encephalopathy (HIE), is estimated to affect up to 0.3% and 4% of full-term and preterm births, respectively 3,4 . The mortality rate in infants with HIE is approximately 15% to 20%.…”

“…The mortality rate in infants with HIE is approximately 15% to 20%. In 25% of HIE survivors, permanent complications arise as a result of the injury, including mental retardation, motor deficits, cerebral palsy, and epilepsy 3,4 . Past therapeutic interventions have not proven worthy of adoption as standard of care, and consensus has yet to be reached that the most advanced methods, based on hypothermia, are effectively reducing morbidity 3,5 .…”