Myelomeningocele (MMC) is a congenital disease without genetic abnormalities. Neurological symptoms are irreversibly impaired after birth. No effective treatment has been reported to date. Only surgical repairs have 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 novel 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.