RESUMEN
Although stem cells are promising candidates for cell replacement therapies, the vast majority are derived using animal sera, which has risk of being contaminated by animal viruses or toxins. To overcome these potential problems, we initially established multiple lines of stem cells from first-trimester human placenta (fPMSC), which were cultivated using human follicular fluid (hFF) instead of fetal bovine serum (FBS). FF provides a very important microenvironment for the development of oocytes. No differences were found in the general morphology, growth rate, karyotype, gene and surface expressions between placental MSCs cultured in 5 % hFF-supplemented medium (fPMSC-X) or 10 % FBS-supplemented medium (fPMSC). Differentiation experiments confirmed similar levels of potency in cells grown in either condition. Since hFF preserved the unique features of the stem cells and is free from potential pathogens, it should be considered as the main culture medium supplement for the propagation of human stem cells for clinical applications.
RESUMEN
Placenta mesenchymal stem cells (PMSCs) have the characteristic features of stem cells including renewability in vitro, surface expression, differentiation potency and ability to adhere to the culture surface. PMSCs expressed genes are normally found in the embryonic tissues before the onset of gastrulation, indicating multipotency. However, the stemness can depend on the stages of the placenta from which the cells were isolated. PMSCs were isolated from two different stages of placenta for comparison, that is the first and third trimesters. Both sets had very similar patterns of surface expression as CD44, CD73, CD90 and CD105, and of self renewability in vitro. Expressions of pluripotency-coupled genes were also confirmed in both sets of cells; however, there was a significant difference in the expression levels: fPMSC (mesenchymal stem cells isolated from the first trimester human placenta) being 2-11-fold higher than tPMSC (mesenchymal stem cells isolated from the third trimester human placenta). Possibly due to the difference in the expression levels of the pluripotency-related genes, induction of genes specific to the ectodermal tissues were more prominent in fPMSC than tPMSC after induced differentiation.
Asunto(s)
Células Madre Mesenquimatosas/fisiología , Placenta/citología , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Ectodermo/citología , Femenino , Expresión Génica , Humanos , Nestina/metabolismo , Neuronas/metabolismo , Embarazo , Primer Trimestre del Embarazo , Tercer Trimestre del EmbarazoRESUMEN
Parkinson's disease (PD) is caused by the progressive loss of dopaminergic neurons in the mesencephalic substantia nigra and is accompanied by behavioral abnormalities. Pharmacological administration of L-dihydroxyphenylalanine (l-dopa) improves the abnormalities in the early phase of the illness, but numerous adverse effects hinder long-term administration. Transplantation of fetal mesencephalic tissues has been suggested as an alternative to l-dopa treatment; however, the use of human fetal tissues is controversial. Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation and are thus a promising substitute for fetal tissue for the replacement of diseased tissues or organs. Previously, this group isolated 17 independent MSCs from the first trimester human placenta (termed first trimester placental MSCs, or fPMSCs) and reported their successful in vitro differentiation into fPMSC-derived neural progenitors (fPMSC-NPs) (Park et al., Placenta 2011; 32:269-276). In the current study, the in vitro-generated fPMSC-NPs were transplanted into the striatum of a rat model of PD to evaluate whether they could undergo terminal differentiation and mediate behavioral recovery. As early as 2 weeks after transplantation, a minor but significant amelioration of rotational asymmetry was observed, and near-normal motor function was achieved at 24weeks. Immunohistochemical and positron emission tomography (PET) analyses provided experimental evidence for the dopaminergic differentiation of the transplanted progenitors. These results show that in vitro-generated fPMSC-NPs are capable of terminal differentiation in vivo and can attenuate motor defects associated with PD. Hence, the placenta is an auspicious source of stem cells for the therapeutic treatment of neurological disorders.