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The establishment of a reliable prenatal source of autologous, transgene-free progenitor cells has enormous potential in the development of regenerative-medicine-based therapies for infants born with devastating birth defects. Here, we show that a largely CD117-negative population of human amniotic fluid mesenchymal stromal cells (AF-MSCs) obtained from fetuses with or without prenatally diagnosed anomalies are readily abundant and have limited baseline differentiation potential when compared with bone-marrow-derived MSCs and other somatic cell types. Nonetheless, the AF-MSCs could be easily reprogrammed into induced pluripotent stem cells (iPSCs) using nonintegrating Sendai viral vectors encoding for OCT4, SOX2, KLF4, and cMYC. The iPSCs were virtually indistinguishable from human embryonic stem cells in multiple assays and could be used to generate a relatively homogeneous population of neural progenitors, expressing PAX6, SOX2, SOX3, Musashi-1, and PSA-NCAM, for potential use in neurologic diseases. Further, these neural progenitors showed engraftment potential in vivo and were capable of differentiating into mature neurons and astrocytes in vitro. This study demonstrates the usefulness of AF-MSCs as an excellent source for the generation of human transgene-free iPSCs ideally suited for autologous perinatal regenerative medicine applications.

Original publication

DOI

10.1089/scd.2014.0110

Type

Journal article

Journal

Stem Cells Dev

Publication Date

01/11/2014

Volume

23

Pages

2613 - 2625

Keywords

Amniotic Fluid, Cell Differentiation, Cell- and Tissue-Based Therapy, Cells, Cultured, Cellular Reprogramming, Eye Proteins, Female, Flow Cytometry, Homeodomain Proteins, Humans, Induced Pluripotent Stem Cells, Kruppel-Like Transcription Factors, Mesenchymal Stem Cells, Microscopy, Fluorescence, Nerve Tissue Proteins, Neural Cell Adhesion Molecule L1, Neural Stem Cells, Octamer Transcription Factor-3, PAX6 Transcription Factor, Paired Box Transcription Factors, Pregnancy, Proto-Oncogene Proteins c-myc, RNA-Binding Proteins, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors, Sialic Acids, Transgenes, Transplantation, Autologous