A potential first in human study of in vitro–derived HSCs. Dermal fibroblasts are collected from a patient with a congenital marrow failure syndrome such as Fanconi anemia. Gene therapy corrects the primary genetic defect. Gene-corrected fibroblasts are used to generate iPSCs by expression of OCT4, SOX2, KLF4, and c-MYC. Hemogenic endothelium is generated in culture, and HSCs are induced by transcription factor transduction. It may be necessary to complete HSC induction and expand these cells in vitro prior to infusion into the patient. Appropriate conditioning regimens must be identified to permit efficient engraftment of these cells while causing minimal toxicity to the patient.