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

Courtney A. McDonald, Margie Castillo-Melendez, Tayla R. Penny, Graham Jenkin and Suzanne L. Miller Margie Castillo-Melendez, Tayla R. Penny, Graham Jenkin and Suzanne L. Miller Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/66647

Courtney A. McDonald,

#### **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.

**Keywords:** cerebral palsy, stem cells, hypoxic-ischemic injury, early intervention, neonatal, fetal growth restriction, Intrauterine growth restriction

## **1. Introduction**

Perinatal brain injury is the underlying cause of cerebral palsy (CP), which is a broad term used to describe deficits in motor function and/or posture. CP affects more than 1 in 450 live births in developed countries and the incidence of severe disability is much higher in low

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

resource countries. There are four principal complications affecting pregnancy or birth that can lead to perinatal brain injury: preterm birth, fetal growth restriction, infection during pregnancy or severe hypoxia-ischemia at birth (birth asphyxia). The time of onset of these complications is different for each condition and other important variables that affect the severity of the resulting brain injury exist. These include the severity of the insult, whether the infant is born preterm or at term and whether complications are compounded (for example, an asphyxic event at birth in a growth restricted infant). Although these complications vary in their fundamental etiology, they share common neuro-pathological features that include hypoxic episodes, inflammation, excitotoxicity and decreased vascular integrity. Umbilical cord blood (UCB)-derived cells demonstrate the potential to mediate these adverse pathways and, thereby, have neuroprotective, neuroregenerative and angiogenic potential for translation into clinical treatments for perinatal brain injury.

UCB is a proven source of hematopoietic stem cells (HSCs) used clinically for treatment of hematological disorders, but it also contains a number of other stem/progenitor cell types, of which mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs), individually or together, offer neuroprotective benefits [1, 2]. Moreover, UCB is also a rich source of immunosupressive cells, such as T regulatory cells (Tregs) and monocyte-derived suppressor cells (MDSCs) [3]. There is supporting evidence that in isolation, each of these cell types have properties that may prevent the progression of hypoxic and inflammatory cascades that drive brain injury; however, their ability to prevent neonatal brain injury has not been well explored. It is likely that each cell type targets different pathways to reduce or repair tissue injury. The study of the properties of whole UCB, as well as its individual cellular components, in animal models of perinatal brain injury is integral towards the development of tailored cell therapy to prevent or repair brain injury in high risk newborn infants. Furthermore, the importance of the timing of administration needs to be further explored. Current clinical trials are administering UCB cells to children that have established CP, with children ranging from 10 months to 20 years old. In contrast, preclinical evidence suggests that administration of UCB cells at an early stage after injury, and while the brain is still plastic and receptive, should be much more effective than later intervention at protecting the brain and promoting brain repair.
