Περίληψη:
Human mesenchymal stem cells (hMSCs) represent a population of multipotent adherent cells able to differentiate into many lineages. In our previous studies, we isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF) and characterized them based on their phenotype, pluripotency and proteomic profile. In the present study, we investigated the plasticity of these cells based on their differentiation, dedifferentiation and transdifferentiation potential in vitro. To this end, adipocyte-like cells (AL cells) derived from AF-MSCs can regain, under certain culture conditions, a more primitive phenotype through the process of dedifferentiation. Dedifferentiated AL cells derived from AF-MSCs (DAF-MSCs), gradually lost the expression of adipogenic markers and obtained similar morphology and differentiation potential to AF-MSCs, together with regaining the pluripotency marker expression. Moreover, a comparative proteomic analysis of AF-MSCs, AL cells and DAF-MSCs revealed 31 differentially expressed proteins among the three cell populations. Proteins, such as vimentin, galectin-1 and prohibitin that have a significant role in stem cell regulatory mechanisms, were expressed in higher levels in AF-MSCs and DAF-MSCs compared with AL cells. We next investigated whether AL cells could transdifferentiate into hepatocyte-like cells (HL cells) directly or through a dedifferentiation step. AL cells were cultured in hepatogenic medium and 4 days later they obtained a phenotype similar to AF-MSCs, and were termed as transdifferentiated AF-MSCs (TRAF-MSCs). This finding, together with the increase in pluripotency marker expression, indicated the adaption of a more primitive phenotype before transdifferentiation. Additionally, we observed that AF-, DAF- and TRAF-MSCs displayed similar clonogenic potential, secretome and proteome profile. Considering the easy access to this fetal cell source, the plasticity of AF-MSCs and their potential to dedifferentiate and transdifferentiate, AF may provide a valuable tool for cell therapy and tissue engineering applications. © 2013 Macmillan Publishers Limited All rights reserved.
Συγγραφείς:
Zagoura, D.S.
Trohatou, O.
Bitsika, V.
Makridakis, M.
Pappa, K.I.
Vlahou, A.
Roubelakis, M.G.
Anagnou, N.P.
Λέξεις-κλειδιά:
galectin 1; initiation factor 3; nucleoside diphosphate kinase A; octamer transcription factor 4; prohibitin; proteome; stage specific embryo antigen 4; transcription factor NANOG; transcription factor Sox2; vimentin; biological marker; galectin 1; prohibitin; repressor protein; vimentin, amnion fluid; article; cell culture; cell dedifferentiation; cell differentiation; cell fate; cell population; cell proliferation; cell therapy; cell transdifferentiation; controlled study; female; human; human cell; in vitro study; liver cell; mesenchymal stem cell; phenotype; priority journal; protein expression; proteomics; second trimester pregnancy; tissue engineering; upregulation; adipocyte; chemistry; culture medium; cytology; gene expression; gene expression profiling; genetics; liver cell; mesenchymal stroma cell; metabolism; pregnancy, Adipocytes; Amniotic Fluid; Biological Markers; Cell Dedifferentiation; Cell Differentiation; Cell Transdifferentiation; Culture Media; Female; Galectin 1; Gene Expression; Gene Expression Profiling; Hepatocytes; Humans; Mesenchymal Stromal Cells; Pregnancy; Pregnancy Trimester, Second; Repressor Proteins; Vimentin
