Mesenchymal stem cells (MSC) are of clinical interest because of their potential use in autologous transplantation. The ability of MSC to differentiate into multiple different cells of mesodermal origin has offered therapeutic tool for the treatment of hematopoietic malignancies and graft versus host disease. Recently, MSC have been shown to ameliorate a variety of neurological dysfunction. This effect is believed to be mediated to their paracrine functions since it is known that MSC produce bioactive substances that promote endogenous neurogenesis. However, the critical question that remains unanswered is whether MSC can transdifferentiate into neural cells. To be “primed” toward a neuronal fate, MSC have to express neural antigens. In an attempt to clarify this issue we explored the constitutive expression of different markers by mesenchymal cells isolated from human umbilical cord Wharton jelly (HUC-MSC) and compare their expression with neural stem cell line derived from human umbilical cord blood (HUCB-NSC) established in our laboratory. Materials and methods: Gene expression pattern in HUC-MSC (passage 5 of cells cultured in MSCGM hMSC Lonza medium) and HUCB-NSC (cultured in DMEM/F12 medium+2% FBS) was performed by real time PCR and RT-PCR reactions. Total RNA was extracted using TRIzol (Invitrogen). Then cDNA was synthesized from total RNA, using High Capacity RNA-to-cDNA kit (Applied Biosystems). PCR reactions were carried out using template cDNA in the presence of specific primers. Concomitantly immunocytochemical analysis of gene-related proteins was employed. The results of our studies have demonstrated that HUC-MSC, in addition to pluripotent (Oct3/4, Nanog1), mesenchymal (CD73, CD90, CD105, CD166) and extracellular matrix (Fibronectin, Vimentin, Collagen1) genes, spontaneously express neural genes i.e. Nestin, NF200, βIIITubulin, MAP2 and GFAP. The initially expressed neuroectodermal genes were comparable with mRNA level of the same neural genes in HUCB-NSC. In addition to neural genes noninduced expression of neural proteins was found. Subsets of HUCMSC were positive for several neural markers, including: Nestin, NF200, βIIITubulin and GFAP. Summary and conclusion: We have demonstrated that MSC derived from human umbilical cord Wharton jelly acquire neural progenitor-like properties by expressing neuronal and astrocytic specific markers. However, it is of clinical interest whether transplanted MSC respond with an appropriate neural pattern of differentiation when exposed to the environment of the host brain. Supported by MSHE grant no N401 014235 and Foundation Jerome Lejeune grant as part of the Novus Sanguis research consortium.
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