Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex

Abstract

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (Ϸ1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker ␤-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

“…Conversely, when cells were grafted following an excitotoxic insult, they were massively present and distributed throughout the lesioned structure. Our observations are also in accordance with the general view that the environment of the diseased brain promotes the survival and migration of grafted stem cells (see Bjorklund and Stenevi, 1984;Sotelo and Alvarado-Mallart, 1987 but also Watts and Dunnett, 1998;Eglitis et al, 1999;Nishino et al, 2000;Mahmood et al, 2001;Imitola et al, 2004;Hill et al, 2004;Kelly et al, 2004;Geloso et al, 2007) and lead us to suggest that at least one factor present within the lesion core promotes the engraftment of these two types of exogenous stem cells of distinct embryonic origins. One such factor could be SCF, shown to be mitogen and chemoattractant for many cells in the hematopoietic system, with the ability to enhance the mobilization of peripheral blood progenitor cells (McNiece and Briddell, 1995;Glaspy, 1996) and to stimulate neurogenesis as well as the migration of endogenous neural stem cells in vivo (Jin et al, 2002;Sun et al, 2004).…”

ABC transporters, neural stem cells and neurogenesis – a different perspective

“…It is still challenging to understand the fate of NSCs in brain lesions [35]. In certain pathologies, such as in stroke lesions, transplanted cells appear to form astrocytes and neurons [36]. Sometimes, a glial fate, even if not ideal, may still be preferred over neural differentiation, as the latter might form abnormal and possibly damaging circuits.…”

HIV-1, chemokines and neurogenesis

“…Indeed, in addition to their role in trafficking leukocytes into the brain, the synthesis of MCP-1 by infarcted areas of the brain has been shown to act as a chemoattractant for mesenchymal progenitor cells in vitro (Wang et al, 2002a,b). Thirdly, two recent publications have demonstrated that progenitor cells migrating into damaged areas of the brain express CXCR4 receptors, and that these receptors are responsible for the targeted migration of these cells (Imitola et al, 2004;Kelly et al, 2004). In both of these recent studies, neural progenitors or a neural progenitor cell line were transplanted into the brain and many cells were shown to migrate towards the site of ischemic brain injury.…”