The neural plasticity of early-passage human bone marrow-derived mesenchymal stem cells and their modulation with chromatin-modifying agents. J Tissue Eng Regen Med 2014 May;8(5):407-13
Date
06/08/2012Pubmed ID
22674835DOI
10.1002/term.1535Scopus ID
2-s2.0-84898480303 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
Mesenchymal stem cells (MSCs) in their immature state express a variety of genes of the three germ layers at relatively low or moderate levels that might explain their phenomenal plasticity. Numerous recent studies have demonstrated that under the appropriate conditions in vitro and in vivo the expression of different sets of these genes can be upregulated, turning MSCs into variety of cell lineages of mesodermal, ectodermal and endodermal origin. While transdifferentiation of MSCs is still controversial, these unique properties make MSCs an ideal autologous source of easily reprogrammable cells. Recently, using the approach of cell reprogramming by biological active compounds that interfere with chromatin structure and function, as well as with specific signalling pathways that promote neural fate commitment, we have been able to generate neural-like cells from human bone marrow (BM)-derived MSCs (hMSCs). However, the efficiency of neural transformation of hMSCs induced by this approach gradually declined with passaging. To elucidate the mechanisms that underlie the higher plasticity of early-passage hMSCs, comparative analysis of the expression levels of several pluripotent and neural genes was conducted for early- and late-passage hMSCs. The results demonstrated that early-passage hMSCs expressed the majority of these genes at low and moderate levels that gradually declined at late passages. Neural induction further increased the expression of some of these genes in hMSCs, accompanied by morphological changes into neural-like cells. We concluded that low and moderate expression of several pluripotent and neural genes in early-passage hMSCs could explain their higher plasticity and pliability for neural induction.
Author List
Zhang Z, Alexanian ARAuthor
Arshak R. Alexanian Adjunct Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blotting, WesternBone Marrow Cells
Cell Shape
Chromatin Assembly and Disassembly
Gene Expression Regulation
Humans
Immunohistochemistry
Neuronal Plasticity
Nuclear Proteins
Real-Time Polymerase Chain Reaction
