Patient-Specific iPSC-Derived Endothelial Cells Provide Long-Term Phenotypic Correction of Hemophilia A

C Olgasi, M Talmon, Simone Merlin, A Cucci, Y Richaud-Patin, G Ranaldo, Donato Colangelo, F Di Scipio, GN Berta, C Borsotti, F Valeri, F Faraldi, M Prat, M Messina, Piercarla Schinco, A Lombardo, A Raya, A Follenzi

Research output: Contribution to journalArticlepeer-review


We generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34+ cells and differentiated them into functional endothelial cells (ECs) secreting factor VIII (FVIII) for gene and cell therapy approaches to cure hemophilia A (HA), an X-linked bleeding disorder caused by F8 mutations. iPSCs were transduced with a lentiviral vector carrying FVIII transgene driven by an endothelial-specific promoter (VEC) and differentiated into bona fide ECs using an optimized protocol. FVIII-expressing ECs were intraportally transplanted in monocrotaline-conditioned non-obese diabetic (NOD) severe combined immune-deficient (scid)-IL2rγ null HA mice generating a chimeric liver with functional human ECs. Transplanted cells engrafted and proliferated in the liver along sinusoids, in the long term showed stable therapeutic FVIII activity (6%). These results demonstrate that the hemophilic phenotype can be rescued by transplantation of ECs derived from HA FVIII-corrected iPSCs, confirming the feasibility of cell-reprogramming strategy in patient-derived cells as an approach for HA gene and cell therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)1391-1406
Number of pages16
JournalStem Cell Reports
Issue number6
Publication statusPublished - 2018


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