Umbilical Cord Blood Cells for Perinatal Brain Injury: The Right Cells at the Right Time?

Abstract

Cerebral palsy (CP) is the most common cause of physical disability in children. CP currently has no cure and there are only few interventions to prevent the development of disability. There are four principal complications of pregnancy or birth that can damage the developing brain and lead to CP: preterm birth, fetal growth restriction, infection during pregnancy and severe hypoxia-ischemia at birth. Umbilical cord blood (UCB) cells are a very promising therapy for the treatment of CP. While UCB therapy for juveniles with CP is currently being assessed in clinical trials, very little is known about their mechanisms of action or which cells found in umbilical cord blood protect against and/ or repair brain injury. In this chapter, we first explore the complications that can lead to perinatal brain injury. We then discuss the different cell types found in UCB and the specific properties that make each of them individually attractive therapeutic candidates for treatment of perinatal brain injury. While UCB holds much promise as a therapy for CP, it is imperative that more research is conducted to understand how the different cell types found in UCB can protect against brain injury in order to design more effective and targeted therapies.

Safety of allogeneic umbilical cord blood infusions for the treatment of neurological conditions: a systematic review of clinical studies

“…The goal of UCB infusion for the treatment of neurological conditions is to provide immunomodulation and paracrine signaling to enhance cell survival in damaged tissues, encourage proliferation of progenitor cells and increase angiogenesis [2,6]. UCB has also been shown to protect against neuroinflammation by suppressing microglial activation and T-cell responses [7]. Notably, cells are proposed to be theoretically efficacious even when the recipient is immune-competent and not myeloablated [8].…”

Human Umbilical Cord Blood Therapy Protects Cerebral White Matter from Systemic LPS Exposure in Preterm Fetal Sheep

“…However, this preclinical animal study is the first to show that human UCB cells are protective for white matter development specifically in response to an inflammatory insult. Human UCB contains a heterogeneous mix of stem and progenitor cells which together, and separately, act in an immunomodulatory, angiogenic, anti-apoptotic and trophic manner for neuroprotective benefits [8,15,20]. The cell types present in UCB include mesenchymal stromal cells, haematopoietic stem cells, endothelial progenitor cells, T regulatory cells, and monocyte-derived suppressor cells [17], with each of these cell types potentially moderating the effects of different injurious cascades, both systemically and in the brain.…”

“…Indeed, there are a number of clinical trials for the examination of UCB in infants and children with CP [15], and results to date support that UCB transplantation in children with established CP is associated with improved motor function with a low risk of adverse events [16]. A significant benefit for the use of UCB cells as a therapeutic intervention reflects the heterogeneous mix of stem cells and progenitor cells, which migrate to sites of injury, promote regeneration, and modulate inflammation [17].…”

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale

“…Umbilical cord blood (UCB) cell therapy is emerging as an exciting and highly promising neuroprotective strategy for neonatal morbidities such as preterm brain injury. UCB cells are enriched with multiple stem and progenitor cell types – each possessing synergistic pleiotropic properties that offer cellular and tissue protection [ 1 ]. The protective properties of UCB cells are likely to be mediated by the paracrine secretion of cytokines, chemokines and growth factors [ 2 ], resulting in immunomodulatory effects [ 3 ].…”