Enhanced green fluorescent protein-expressing human mesenchymal stem cells retain neural marker expression.
ABSTRACT Mesenchymal stem cells (MSCs) have the potential to play a role in autologous treatment of central nervous system injury or disease. Here we transduced human MSCs with enhanced green fluorescent protein (EGFP). We compared the capacity of control and EGFP-positive cells to proliferate under normal culture conditions, as well as express neural markers following trans-differentiation. EGFP-positive cells proliferated comparably to controls, retained EGFP expression over the course of multiple passages, and retained neural marker expression at levels comparable to control MSCs. Further neurogenic capacity of EGFP-positive human MSCs was examined by growth as neural stem cell-like neurospheres. No significant difference was observed in the ability of control or EGFP-positive cells to generate primary neurospheres or to expand during passage. When examined by immunostaining for the presence of neuroectodermal markers, neurosphere-derived cells similarly expressed neural markers. We show that human MSCs expressing EGFP represent an attractive and practical source of stem cells for the study of repair and regeneration in neurological models.
Full-textDOI: · Available from: James B Uney, May 30, 2015
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ABSTRACT: Mesenchymal stem cells (MSCs) can abrogate the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), but whether this therapeutic effect occurs entirely through systemic immune modulation and whether CNS infiltration occurs after peripheral delivery are uncertain. We studied the clinical and neuropathologic effects of intravenously administered human MSCs (hMSCs) in C57BL/6 mice with EAE. Human MSCs significantly reduced the clinical disease severity, particularly in later disease. Large numbers of hMSCs migrated into gray and white matter at all levels of the spinal cord in both naive mice and mice with EAE. In the latter, hMSCs accumulated over time in demyelinated areas. There were 2 distinct morphological appearances of the hMSCs in the tissue, that is, rounded and less numerous process-bearing forms; very few expressed neural markers. The number of spinal cord white matter lesions and areas of white matter demyelination were reduced after hMSC treatment compared with control treatment. These findings show that central nervous system infiltration occurs after peripheral delivery of hMSCs, that they accumulate where there is myelin damage, and that they are associated with a reduced extent of demyelination. These data support a potential role for hMSCs in autologous cell therapy in multiple sclerosis.Journal of Neuropathology and Experimental Neurology 10/2010; 69(11):1087-95. DOI:10.1097/NEN.0b013e3181f97392 · 4.37 Impact Factor
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ABSTRACT: In addition to traditional osteogenic, chondrogenic, and adipogenic differentiation, mesenchymal stem cells are considered to be capable of also giving rise to neural lineage. We overview the transgenic approach for the neurogenic differentiation of MSCs, including the expression of neurotrophic factors, signaling molecules, and other transgenes with neurogenic properties. Key wordsmesenchymal stem cells-neurogenic differentiation-transgene-transductionCell and Tissue Biology 08/2010; 4(4):309-312. DOI:10.1134/S1990519X10040012
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ABSTRACT: Modern medicine will unequivocally include regenerative medicine as a major breakthrough in the re-establishment of damaged or lost tissues due to degenerative diseases or injury. In this scenario, millions of patients worldwide can have their quality of life improved by stem cell implantation coupled with endogenous secretion or administration of survival and differentiation promoting factors. Large efforts, relying mostly on flow cytometry and imaging techniques, have been put into cell isolation, immunophenotyping, and studies of differentiation properties of stem cells of diverse origins. Mesenchymal stem cells (MSCs) are particularly relevant for therapy due to their simplicity of isolation. A minimal phenotypic pattern for the identification of MSCs cells requires them to be immunopositive for CD73, CD90, and CD105 expression, while being negative for CD34, CD45, and HLA-DR and other surface markers. MSCs identified by their cell surface marker expression pattern can be readily purified from patient's bone marrow and adipose tissues. Following expansion and/or predifferentiation into a desired tissue type, stem cells can be reimplanted for tissue repair in the same patient, virtually eliminating rejection problems. Transplantation of MSCs is subject of almost 200 clinical trials to cure and treat a very broad range of conditions, including bone, heart, and neurodegenerative diseases. Immediate or medium term improvements of clinical symptoms have been reported as results of many clinical studies. © 2012 International Society for Advancement of Cytometry.Cytometry Part A 01/2013; 83A(1). DOI:10.1002/cyto.a.22205 · 3.07 Impact Factor