Abstract
We have recently characterized a stem cell population isolated from the rodent amniotic membrane termed amnion-derived stem cells (ADSCs). In vitro ADSCs differentiate into cell types representing all three embryonic layers, including neural cells. In this study we evaluated the neuroectodermal potential of ADSCs in vivo after in utero transplantation into the developing rat brain. A clonal line of green fluorescent protein-expressing ADSCs were infused into the telencephalic ventricles of the developing embryonic day 15.5 rat brain. At E17.5 donor cells existed primarily as spheres in the ventricles with subsets fused to the ventricular walls, suggesting a mode of entry into the brain parenchyma. By E21.5 green fluorescent protein (GFP) ADSCs migrated to a number of brain regions. Examination at postnatal time points revealed that donor ADSCs expressed vimentin and nestin. Subsets of transplanted ADSCs attained neuronal morphologies, although there was no immunohistochemical evidence of neural or glial differentiation. Some donor cells migrated around blood vessels and differentiated into putative endothelial cells. Donor ADSCs transplanted in utero were present in recipients into adulthood with no evidence of immunological rejection or tumour formation. Long-term survival may suggest utility in the treatment of disorders where differentiation to a neural cell type is not required for clinical benefit.
Highlights
Stem cells have been touted as potential therapeutic agents for a wide spectrum of degenerative diseases from Parkinson’s disease to lysosomal storage diseases
We explore the plasticity of amnion-derived stem cells (ADSCs) in vivo, examining their potential to migrate, engraft, survive long-term, and differentiate into neuroectodermal cell types after in utero transplantation
For transplantation studies we utilized a clonal population of ADSCs which uniformly expressed green fluorescent protein (GFP) (Fig. 1A–C)
Summary
Stem cells have been touted as potential therapeutic agents for a wide spectrum of degenerative diseases from Parkinson’s disease to lysosomal storage diseases. Extra-embryonic tissue, such as placenta [1, 2] and umbilical cord [3,4,5,6], have received a great deal of attention as alternative sources of multipotent stem cells for therapeutic use. Extra-embryonic stem cells are attractive for neural transplant strategies. Transplantation of Recently, we have used a tissue explant method to isolate a stem cell population from the rat amniotic membrane, termed ADSCs. ADSCs are capable of extensive self-renewal and exist in culture in a multi-differentiated state, expressing neuroectodermal (nestin), mesodermal (vimentin and fibronectin) and endodermal (␣-1-antitrypsin) genes. ADSCs differentiate into putative neural cells in vitro after culture in a defined neural induction media [10]. To determine whether the neuroectodermal potential observed in culture correlates doi:10.1111/j.1582-4934.2007.00180.x
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