Stem cells for neonatal stroke- the future is here.

Abstract

STEM CELLS In recent years stem cell therapy has emerged as a potential treatment for neonatal ischemic brain injury. The efficacy of cellbased therapies in restoring damaged brain tissue has been tested in a multitude of models for different CNS diseases. Several different stem and progenitor cell populations have been utilized as cell-based therapy, including neural stem cells, embryonic stem cells, human umbilical cord blood cells (HUBCs), hematopoietic stem and progenitor cells, and mesenchymal stem cells (MSCs). Most stem cell types appear to enhance recovery to some extent (Pimentel-Coelho and Mendez-Otero, 2010). However, because of their low immunogenicity, availability and positive results obtained from preclinical studies, MSCs are a particularly promising candidate to repair the devastating effects that are associated with neonatal stroke. MSCs were first isolated and identified in bone marrow, but can now be isolated from many tissues, including adipose tissue, muscle, skin and extraembryonic tissues like the placenta, umbilical cord and Wharton’s jelly. The latter sources are of particular interest for neonates that experience an ischemic event around the time of birth, at which time cells can be harvested and transplanted from an autologous source. MSCs derived from different sources have slightly different characteristics, but as of yet it is unknown whether this influences their therapeutic potential. Our group and others have shown that administration of MSCs reduces lesion volume, provides positive effects on the white matter and improves motor function (van Velthoven et al., 2012). Numerous studies have been done under the premise that transplanted stem cells contribute to brain repair by directly replacing damaged or lost tissue. While there is evidence that transplanted cells undergo differentiation toward neuronal lineages, improved outcomes have been observed even when survival of transplanted cells is low and engrafted cells are absent. This suggests that rather than replacing damaged cells, transplanted cells may improve outcome via indirect mechanisms. For example, MSCs have been shown to secrete many factors that can influence important processes like apoptosis, neurogenesis, angiogenesis and synaptogenesis.