Human transgene-free amniotic-fluid-derived induced pluripotent stem cells for autologous cell therapy

Guihua Jiang, Julie Di Bernardo, Michael M. Maiden, Luis G. Villa-Diaz, Omar S. Mabrouk, Paul H. Krebsbach, K. Sue O'shea, Shaun M. Kunisaki

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish (US)
Pages (from-to)2613-2625
Number of pages13
JournalStem Cells and Development
Volume23
Issue number21
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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