Arshak R Alexanian1. 1. Neuroscience Research Laboratories, Department of Neurosurgery, VA Medical Center - Research 151, 5000 West National Avenue, Milwaukee, Wisconsin, WI 53295, USA. aalexan@mcw.edu
Abstract
BACKGROUND: Stem cell-based therapies to repair and replace lost neural cells are a highly promising treatment for CNS diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) have great potential as therapeutic agents against neurological maladies, since they have the ability to differentiate into neural phenotypes and can be readily isolated and expanded for autotransplantation with no risk of rejection. In our previous studies, we demonstrated that neural cells could be efficiently generated from mouse BM-derived MSCs by exposing cells to epigenetic modifiers and a neural environment. The main idea of this approach was the reactivation of pluripotency-associated genes in MSCs before exposing them to neural-inducing factors. AIM: In this study, we used a similar approach to efficiently generate neural cells from human BM-derived MSCs. METHOD: Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation and histone deacetylation, and pharmacological agents that increase cAMP levels. RESULTS: The expression of pluripotency and neural markers was confirmed with immunocytochemistry, western blot and real-time PCR. ELISA studies showed that these neurally induced-human MSCs cells released the neurotrophic factors glial cell-derived neurotrophic factor and brain-derived neurotrophic factor. CONCLUSION: Human MSCs that are neurally modified with this methodology could be a useful source of cells for CNS repair and regeneration.
BACKGROUND: Stem cell-based therapies to repair and replace lost neural cells are a highly promising treatment for CNS diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) have great potential as therapeutic agents against neurological maladies, since they have the ability to differentiate into neural phenotypes and can be readily isolated and expanded for autotransplantation with no risk of rejection. In our previous studies, we demonstrated that neural cells could be efficiently generated from mouse BM-derived MSCs by exposing cells to epigenetic modifiers and a neural environment. The main idea of this approach was the reactivation of pluripotency-associated genes in MSCs before exposing them to neural-inducing factors. AIM: In this study, we used a similar approach to efficiently generate neural cells from human BM-derived MSCs. METHOD: Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation and histone deacetylation, and pharmacological agents that increase cAMP levels. RESULTS: The expression of pluripotency and neural markers was confirmed with immunocytochemistry, western blot and real-time PCR. ELISA studies showed that these neurally induced-human MSCs cells released the neurotrophic factors glial cell-derived neurotrophic factor and brain-derived neurotrophic factor. CONCLUSION:Human MSCs that are neurally modified with this methodology could be a useful source of cells for CNS repair and regeneration.
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