title: Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients.
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Tanapol
authors.initials: T
authors.lastname: Phondeechareon
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Methichit
authors.initials: M
authors.lastname: Wattanapanitch
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Yaowalak
authors.initials: Y
authors.lastname: U-Pratya
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chanapa
authors.initials: C
authors.lastname: Damkham
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nuttha
authors.initials: N
authors.lastname: Klincumhom
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chanchao
authors.initials: C
authors.lastname: Lorthongpanich
authors.affiliation: Division of Cell Biology, Department of Pre-clinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Pakpoom
authors.initials: P
authors.lastname: Kheolamai
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chuti
authors.initials: C
authors.lastname: Laowtammathron
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. surapolsi@gmail.com.|Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. surapolsi@gmail.com.
authors.forename: Surapol
authors.initials: S
authors.lastname: Issaragrisil
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D018958:CD55 Antigens / Q000096:biosynthesis; D018957:CD59 Antigens / Q000096:biosynthesis; D000067470:Cellular Reprogramming Techniques; D058732:Embryoid Bodies; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D006457:Hemoglobinuria, Paroxysmal / Q000628:therapy*; D049669:History, 16th Century; D049670:History, 17th Century; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D051917:Leukosialin / Q000096:biosynthesis; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012867:Skin / Q000166:cytology; D013724:Teratoma / Q000473:pathology; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D018958:CD55 Antigens; D018957:CD59 Antigens; D051917:Leukosialin; C465014:SPN protein, human
keywords: Hematopoietic cell differentiation; Hematopoietic stem cells; Induced pluripotent stem cells; Paroxysmal nocturnal hemoglobinuria