Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

Abstract

Bone marrow stromal stem cells (MSCs) normally differentiate into mesenchymal derivatives but recently have also been converted into neurons, classical ectodermal cells. To begin defining underlying mechanisms, we extended our characterization of MSCs and the differentiated neurons. In addition to expected mesodermal mRNAs, populations and clonal lines of MSCs expressed germinal, endodermal, and ectodermal genes. Thus, the MSCs are apparently "multidifferentiated" in addition to being multipotent. Conversely, the differentiating neurons derived from populations and clonal lines of MSCs expressed the specific markers ␤-III tubulin, tau, neurofilament-M, TOAD-64, and synaptophysin de novo. The transmitter enzymes tyrosine hydroxylase and choline acetyltransferase were localized to neuronal subpopulations. Our observations suggest that MSCs are already multidifferentiated and that neural differentiation comprises quantitative modulation of gene expression rather than simple on-off switching of neural-specific genes.

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

“…S3a). When MSCs were subjected to the preinduction medium followed by MNM as described previously [13,35,36], they rapidly underwent dramatic morphological changes. Within a few hours, large number of the cells rounded up and showed thin radial processes reminiscent of neurites (Supporting Information Fig.…”

“…However, recent studies have provided evidence that terminally differentiated mammalian cells can undergo dedifferentiation on injury [29,30] or when the cells are cultured under special conditions [30][31][32][33][34]. Previous studies from both our group and others have demonstrated that on withdrawal of extrinsic stimulation, MSC-derived neurons are able to revert back to MSC morphologically [35,36]. However, the question as to whether the dedifferentiated MSCs (De-MSCs) are identical to or different from their original counterparts has not been addressed and their therapeutic potential is not explored.…”

Epigenetics and the plasticity of differentiation in normal and cancer stem cells

“…Results with hematopoietic stem cells and CD34 positive hematopoietic progenitors have shown, that these cells express genes that are expressed in neural and various other normal nonhematopoietic tissues (Luce and Burrows, 1999;Akashi et al, 2003;Goolsby et al, 2003;Georgantas et al, 2004;Steidl et al, 2004). Skeletal muscle stem cells express neural stem cell genes and adult bone marrow-derived mesenchymal stem cells express different mesenchymal genes as well as genes of various other lineages including neuronal, testis, liver, lung, hematopoietic and endothelial tissues (Woodbury et al, 2002;Seshi et al, 2003). The differentiation plasticity of adult stem cells, like in ES cells, is thus associated with transcription accessibility for genes that are normally preferentially expressed in different tissues (Table 1).…”

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

“…[23][24][25] Furthermore, it has been reported that MSCs can manifest multiple neural phenotypes even without neurogenic stimulation. 26 Moreover, in a rat cerebral ischemia model, intracranially implanted MSCs can migrate away from the initial injection site towards an infarction without changing morphologically to a neural phenotype. 25 Taken together, these findings imply that NSCs could be replaceable with MSCs as a therapeutic vehicle for gene therapy against glioma.…”