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

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.

• Authors: Kazuhiro Kajiwara, Tomohiro Tanemoto, Seiji Wada, Jurii Karibe, Norimasa Ihara, Yu Ikemoto, Tomoyuki Kawasaki, Yoshie Oishi, Osamu Samura, Kohji Okamura, Shuji Takada, Hidenori Akutsu, Haruhiko Sago, Aikou Okamoto, Akihiro Umezawa
• Journal: Stem cell reports (Stem Cell Reports) Vol. 8 Issue 6 Pg. 1701-1713 (06 06 2017) ISSN: 2213-6711 [Electronic] United States
• PMID: 28591652 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Amides
• CRELD1 protein, human
• Cell Adhesion Molecules
• Extracellular Matrix Proteins
• Keratin-14
• Pyridines
• Transcription Factors
• Y 27632
• Epidermal Growth Factor

Topics

• Amides (pharmacology)
• Amniotic Fluid (cytology)
• Animals
• Cell Adhesion Molecules (genetics)
• Cell Culture Techniques
• Cell Differentiation (drug effects)
• Cells, Cultured
• Cellular Reprogramming
• Disease Models, Animal
• Down Syndrome (pathology)
• Epidermal Cells
• Epidermal Growth Factor (pharmacology)
• Epidermis (metabolism)
• Extracellular Matrix Proteins (genetics)
• Female
• Fetal Therapies
• Fetofetal Transfusion (therapy)
• Humans
• Induced Pluripotent Stem Cells (cytology, metabolism, transplantation)
• Karyotyping
• Keratin-14 (metabolism)
• Keratinocytes (cytology, drug effects, metabolism)
• Meningomyelocele (pathology, therapy)
• Polymorphism, Single Nucleotide
• Pregnancy
• Pyridines (pharmacology)
• Rats
• Skin (pathology)
• Transcription Factors (genetics, metabolism)
• Exome Sequencing