4.2 Review

Preventing Brain Damage from Hypoxic-Ischemic Encephalopathy in Neonates: Update on Mesenchymal Stromal Cells and Umbilical Cord Blood Cells

Journal

AMERICAN JOURNAL OF PERINATOLOGY
Volume 39, Issue 16, Pages 1754-1763

Publisher

THIEME MEDICAL PUBL INC
DOI: 10.1055/s-0041-1726451

Keywords

hypoxic– ischemic encephalopathy; cerebral palsy; umbilical cord blood stem cells; mesenchymal stromal cells; HIE; CP; MSCs; secondary energy failure

Funding

  1. Japan Agency for Medical Research and Development for autologous UCB

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The review discusses the brain damage process caused by neonatal HIE, introduces the roles of TH and cell therapies in protecting the newborn brain, and recent progress in using UC-MSCs for treating neurological disorders.
Objective Neonatal hypoxic-ischemic encephalopathy (HIE) causes permanent motor deficit cerebral palsy (CP), and may result in significant disability and death. Therapeutic hypothermia (TH) had been established as the first effective therapy for neonates with HIE; however, TH must be initiated within the first 6 hours after birth, and the number needed to treat is from 9 to 11 to prevent brain damage from HIE. Therefore, additional therapies for HIE are highly needed. In this review, we provide an introduction on the mechanisms of HIE cascade and how TH and cell therapies such as umbilical cord blood cells and mesenchymal stromal cells (MSCs), especially umbilical cord-derived MSCs (UC-MSCs), may protect the brain in newborns, and discuss recent progress in regenerative therapies using UC-MSCs for neurological disorders. Results The brain damage process HIE cascade was divided into six stages: (1) energy depletion, (2) impairment of microglia, (3) inflammation, (4) excitotoxity, (5) oxidative stress, and (6) apoptosis in capillary, glia, synapse and/or neuron. The authors showed recent 13 clinical trials using UC-MSCs for neurological disorders. Conclusion The authors suggest that the next step will include reaching a consensus on cell therapies for HIE and establishment of effective protocols for cell therapy for HIE.

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