An efficient method for generation of neural-like cells from adult human bone marrow-derived mesenchymal stem cells. Regen Med 2010 Nov;5(6):891-900
Date
11/19/2010Pubmed ID
21082889DOI
10.2217/rme.10.67Scopus ID
2-s2.0-78649352249 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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.
Author List
Alexanian ARAuthor
Arshak R. Alexanian VMD, PhD Adjunct Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAdult Stem Cells
Blotting, Western
Bone Marrow Cells
Cell Culture Techniques
Cell Differentiation
Cell Shape
Gene Expression Regulation
Humans
Immunohistochemistry
Neurons
Reverse Transcriptase Polymerase Chain Reaction
Staining and Labeling