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U. Vossmerbaeumer, S. Kuehl, S. Kern, H. Kluter, I. Kreissig, J.B. Jonas, K. Bieback; Plasticity of Mesenchymal Stem Cells for Differentiation Into RPE–Like Neuroectodermal Lineage . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4192.
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© ARVO (1962-2015); The Authors (2016-present)
Mesenchymal stem cells (MSC) from adipose tissue (AT) have been shown to be differentiable into various cell types of the mesodermal lineage. Whether these cells have the potential to differentiate into cells of the neuroectodermal lineage, however, is a matter of intense debate. We investigate if it is possible to induce a retinal pigment epithelium (RPE) phenotype in these uncomitted AT–derived MSC.
MSC from human lipoaspirate were cultured in MSC growth promoting medium. MSC properties were ascertained by assays for mesodermal differentiation and FACS analysis for stem cell specific surface antigen patterns. Differentiation towards RPE lineage was triggered by exposure to conditioned media from porcine RPE cells, and/or Vasoactive Intestinal Peptide (VIP). Resulting cell populations were assessed for quantitative and qualitative expression of RPE–specific markers. Functional analysis included melanin synthesis.
AT–derived MSC were tested positive for an MSC typical array of CD markers. Their potential to differentiate along the mesodermal lineage was assessed using adipo–, osteo– and chondrogenic differentiation assays. Induction of differentiation into RPE–like cells by conditioned medium and/or VIP led to expression of RPE markers Bestrophin (77.6–88.9%), Cytokeratine 8/18 (52.6–57.6%) and RPE 65 (57.44–61.26%) irrespective of the culture condition used. Subsequent functional assessment of formation of brown granules proved melanin synthesis switched on by melanocyte stimulating hormone treatment.
The results suggest that AT–derived MSC may be induced to differentiate into RPE–like cells. Beyond the expression of typical RPE markers, cells displayed functional capacities of RPE cells like formation of brown granules as sign of melanin synthesis. The finding of AT–derived MSC plasticity for differentiation into RPE–like cells (neuroectodermal) may be interesting for an autologous cell therapy in age–related macular degeneration.
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