Migration and fate of therapeutic stem cells in different brain disease models

Abstract

Stem cells have a number of properties, which make them excellent candidates for the treatment of various neurologic disorders, the most important of which being their ability to migrate to and differentiate predictably at sites of pathology in the brain. The disease-directed migration and well-characterized differentiation patterns of stem cells may eventually provide a powerful tool for the treatment of both localized and diffuse disease processes within the human brain. A thorough understanding of the molecular mechanisms governing their migratory properties and their choice between different differentiation programs is essential if these cells are to be used therapeutically in humans. This review focuses on summarizing the migration and differentiation of therapeutic neural and mesenchymal stem cells in different disease models in the brain and also discusses the promise of these cells to eventually treat various forms of neurologic disease.

Modulation properties of factors released by bone marrow stromal cells on activated microglia: an in vitro study

“…BMSCs factors are known to ameliorate disease in various animal models of neuroinflammation could control in vitro SCI-CM–induced BV2 chemotaxis2958, NO release, as well as morphological changes in activated microglia. Similarly to microglia, BMSCs are attracted towards areas of tissue damage, indicating that microglia may primarily serve as a homing signal61. Here we show that BMSCs-soluble factors significantly down-regulated SCI-CM-induced BV2 and PM migration, which confirms their modulatory properties5860.…”

“…Our results provide further evidence of a link between migratory response and morphological changes in microglial cells upon exposure to different conditioned media. SCI-CM (lesion site) served as a strong trigger for microglia migration and also caused BV2 cell transformation from round-shaped, semi-adherent cell lines into adherent, stellate–like or long bipolar cells with filopodia production61, revealing typical inflammatory response during the entire time period. However, BMSCs that clearly attenuated microglia migration showed time-dependent cytotoxic effects on BV2 cells.…”

Emerging insights into the molecular and cellular basis of glioblastoma

“…Conventional malignant glioma cell lines do not tend to exhibit invasive growth in orthotopic xenograft models, but tumor-initiating cells not only invade (Singh et al 2004;Wong et al 2011), but also often phenocopy the type of invasion observed radiographically in patients from which the cells were derived (Wakimoto et al 2012), thereby representing high-fidelity platforms to explore invasion (Bhat et al 2011). Furthermore, the striking, but poorly understood, migratory capacity of neural and mesenchymal stem cells in transplant models (Carney and Shah 2011) affords another invasive model that can be used to interrogate this process.…”

CD117+amniotic fluid stem cells

“…Stem cells represent a promising therapeutic strategy for the cure of different neurologic diseases including neurodegenerative disorders and central nervous system acute injuries. 88,89 The demonstration that AFS cells are capable of entering the neuroectodermal lineage in neuronal conditions was given in 2007. Monoclonal CD117+ human AFS cells were induced to differentiate upon the neurogenic lineage as proven by specific marker expression (e.g., GIRK potassium channels), morphology changes, exhibition of barium-sensitive potassium current and glutamate release after stimulation.…”