Human Transgene-Free Amniotic-Fluid-Derived Induced Pluripotent Stem Cells for Autologous Cell Therapy

Autor: Julie Di Bernardo, K. Sue O'Shea, Shaun M. Kunisaki, Luis G. Villa-Diaz, Omar S. Mabrouk, Guihua Jiang, Paul H. Krebsbach, Michael M. Maiden
Rok vydání: 2014
Předmět:
Amniotic fluid
PAX6 Transcription Factor
Induced Pluripotent Stem Cells
Cell- and Tissue-Based Therapy
Kruppel-Like Transcription Factors
Nerve Tissue Proteins
Neural Cell Adhesion Molecule L1
Biology
Transplantation
Autologous
Proto-Oncogene Proteins c-myc
Kruppel-Like Factor 4
Neural Stem Cells
Pregnancy
Humans
Paired Box Transcription Factors
Transgenes
Progenitor cell
Eye Proteins
Induced pluripotent stem cell
Cells
Cultured
Homeodomain Proteins
Induced stem cells
Reverse Transcriptase Polymerase Chain Reaction
SOXB1 Transcription Factors
RNA-Binding Proteins
Cell Differentiation
Mesenchymal Stem Cells
Amniotic stem cells
Cell Biology
Hematology
Amniotic Fluid
Cellular Reprogramming
Flow Cytometry
Repressor Proteins
Endothelial stem cell
Microscopy
Fluorescence
Amniotic epithelial cells
Immunology
Sialic Acids
Cancer research
Female
Stem cell
Octamer Transcription Factor-3
Developmental Biology
Zdroj: Stem Cells and Development. 23:2613-2625
ISSN: 1557-8534
1547-3287
DOI: 10.1089/scd.2014.0110
Popis: 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.
Databáze: OpenAIRE
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