Human Mesenchymal Stem Cells Signals Regulate Neural Stem Cell Fate
ABSTRACT Neural stem cells (NSCs) differentiate into neurons, astrocytes and oligodendrocytes depending on their location within the central nervous system (CNS). The cellular and molecular cues mediating end-stage cell fate choices are not completely understood. The retention of multipotent NSCs in the adult CNS raises the possibility that selective recruitment of their progeny to specific lineages may facilitate repair in a spectrum of neuropathological conditions. Previous studies suggest that adult human bone marrow derived mesenchymal stem cells (hMSCs) improve functional outcome after a wide range of CNS insults, probably through their trophic influence. In the context of such trophic activity, here we demonstrate that hMSCs in culture provide humoral signals that selectively promote the genesis of neurons and oligodendrocytes from NSCs. Cell-cell contacts were less effective and the proportion of hMSCs that could be induced to express neural characteristics was very small. We propose that the selective promotion of neuronal and oligodendroglial fates in neural stem cell progeny is responsible for the ability of MSCs to enhance recovery after a wide range of CNS injuries.
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ABSTRACT: Recent studies of Autism Spectrum Disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.Medical Hypotheses 12/2014; 84(3). DOI:10.1016/j.mehy.2014.12.016 · 1.15 Impact Factor
Dataset: Skoloudik Chrobok 2014
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ABSTRACT: Multipotent mesenchymal stromal cells (MSCs) are primitive cells capable of restoring damaged mesenchyme and with the ability to differentiate into mature cells of bone, cartilage, muscle, fat, nerve or fibrous tissues. MSCs are therefore good candidates for applications in regenerative medicine and cell based therapy. They regenerate through self-renewal, differentiational capacity, immune modulation and secretion of bioactive molecules. Authors present a review of MSCs applications in otorhinolaryngology. The major interest is focused on phonosurgery, sensorineural deafness and reconstruction of large tissue defects with bone, cartilage or soft tissue replacement. Current evidence of MSCs treatment efficacy in otorhinolaryngology is based on animal models. The true impact on clinical treatment will not be known until clinical studies prove functional outcomes in human medicine.Medical Hypotheses 03/2014; 82(6):769-773. DOI:10.1016/j.mehy.2014.03.022 · 1.15 Impact Factor