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

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

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.

MeSH terms

  • 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
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation*
  • Karyotyping
  • Keratin-14 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Meningomyelocele / pathology
  • Meningomyelocele / therapy*
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Pyridines / pharmacology
  • Rats
  • Skin / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Whole Exome Sequencing

Substances

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