The Properties Of Dedifferentiated Placenta Derived Mesenchymal Stem Cells And The Potentiai Mechanisms During Differentiation And Dedifferentiation

BackgroundStem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) have been widely used in various areas including researches and clinical tests, and they were deemed as effective therapies for terminal diseases. ESCs, which are isolated from embryo, can be induced to various somatic cells, while the clinical usage of ESCs is inhibited by ethical problems. iPSCs are reprogrammed from somatic cells with transcriptional factors, while the clinical usage of them is inhibited by tumorigenesis. MSCs, which are fibroblast-like, plastic and self-renewing cells, can be differentiated to various functional cells. MSCs can be applied to cell transplantation, bioartificial liver and so on, but the cell resource still requires to be supplied.MSCs can be isolated from bone marrow, adipose, placenta, umbilical cord blood, umbilical cord and so on. Placenta derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and trans-differentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type or the differentiated cell type is unknown to us; meanwhile, the detailed mechanisms during differentiation and dedifferentiation are still unclarified.MethodsIn this study, we induced PDMSCs to adipocytes or hepatocytes for several days, the inductive medium was replaced by general culture medium. After that, we investigated the expression of mesenchymal markers and embryonic markers; at the same time, the mitochondrial biogenesis during these processes was also investigated. We compared the proliferative ability and multilineage potency of dedifferentiated PDMSCs with uncommitted PDMSCs. We intended to find different genes in the two processes by affymetrix primeview human gene expression array. Then the different genes were uploaded to DAVID 6.7 database, furthermore, KEGG pathways were analyzed for the potential mechanisms.ResultsWe showed that after withdrawing the extrinsic factors, adipogenic or hepatogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The morphology, mesenchymal markers, embryonic markers, mitochondrial network turned back to a primitive level after dedifferentiation. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. By comparing different genes during the differentiation and dedifferentiation processes, we clarified that some signaling pathways including pathways in cancer, cell adherison molecules and cell cycle mainly regulated the dedifferentiation processes.ConclusionsAfter dedifferentiation of the differentiated PDMSCs, the new population can proliferate faster than uncommitted PDMSCs. Furthermore, the multilineage potency was maintained after the dedifferentiation. There existed different signaling pathways including pathways in cancer, cell adherison molecules and cell cycle in the differentiation and dedifferentiation processes. These observations indicated that the dedifferentiated PDMSCs were distinguishable with the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies.