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Stem Cell Reports. 2017 Jun 6;8(6):1701-1713. doi: 10.1016/j.stemcr.2017.05.013.

Fetal Therapy Model of Myelomeningocele with Three-Dimensional Skin Using Amniotic Fluid Cell-Derived Induced Pluripotent Stem Cells.

Author information

1
Department of Reproductive Biology, Center for Regenerative Medicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan; Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8471, Japan.
2
Department of Medical Science, Chiba University Graduate School of Medicine, Chiba 260-0856, Japan.
3
Maternal-Fetal, Neonatal and Reproductive Medicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
4
Department of Reproductive Biology, Center for Regenerative Medicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan.
5
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8471, Japan.
6
Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
7
Department of Reproductive Biology, Center for Regenerative Medicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan. Electronic address: umezawa@1985.jukuin.keio.ac.jp.

Abstract

Myelomeningocele (MMC) is a congenital disease without genetic abnormalities. Neurological symptoms are irreversibly impaired after birth, and no effective treatment has been reported to date. Only surgical repairs have been reported so far. In this study, we performed antenatal treatment of MMC with an artificial skin using induced pluripotent stem cells (iPSCs) generated from a patient with Down syndrome (AF-T21-iPSCs) and twin-twin transfusion syndrome (AF-TTTS-iPSCs) to a rat model. We manufactured three-dimensional skin with epidermis generated from keratinocytes derived from AF-T21-iPSCs and AF-TTTS-iPSCs and dermis of human fibroblasts and collagen type I. For generation of epidermis, we developed a protocol using Y-27632 and epidermal growth factor. The artificial skin was successfully covered over MMC defect sites during pregnancy, implying a possible antenatal surgical treatment with iPSC technology.

KEYWORDS:

amniotic fluid; epidermal growth factor; fetal therapy; induced pluripotent stem cells; keratinocytes; myelomeningocele; polyhydramnion; rock inhibitor

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