Jungmin Lee1, Brad Dykstra, Robert Sackstein, Derrick J Rossi. 1. aDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge bProgram in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital cDepartment of Dermatology, and Program of Excellence in Glycosciences, Brigham & Women's Hospital, Harvard Medical School dDivision of Hematology, Department of Medicine, Brigham & Women's Hospital eDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston fHarvard Stem Cell Institute, Cambridge, Massachusetts, USA *Jungmin Lee and Brad Dykstra contributed equally to the writing of this manuscript.
Abstract
PURPOSE OF REVIEW: Human pluripotent stem cells (PSCs) have the potential to provide an inexhaustible source of hematopoietic stem cells (HSCs) that could be used in disease modeling and in clinical applications such as transplantation. Although the goal of deriving definitive HSCs from PSCs has not been achieved, recent studies indicate that progress is being made. This review will provide information on the current status of deriving HSCs from PSCs, and will highlight existing challenges and obstacles. RECENT FINDINGS: Recent strides in HSC generation from PSCs has included derivation of developmental intermediates, identification of transcription factors and small molecules that support hematopoietic derivation, and the development of strategies to recapitulate niche-like conditions. SUMMARY: Despite considerable progress in defining the molecular events driving derivation of hematopoietic progenitor cells from PSCs, the generation of robust transplantable HSCs from PSCs remains elusive. We propose that this goal can be facilitated by better understanding of the regulatory pathways governing HSC identity, development of HSC supportive conditions, and examining the marrow homing properties of PSC-derived HSCs.
PURPOSE OF REVIEW: Human pluripotent stem cells (PSCs) have the potential to provide an inexhaustible source of hematopoietic stem cells (HSCs) that could be used in disease modeling and in clinical applications such as transplantation. Although the goal of deriving definitive HSCs from PSCs has not been achieved, recent studies indicate that progress is being made. This review will provide information on the current status of deriving HSCs from PSCs, and will highlight existing challenges and obstacles. RECENT FINDINGS: Recent strides in HSC generation from PSCs has included derivation of developmental intermediates, identification of transcription factors and small molecules that support hematopoietic derivation, and the development of strategies to recapitulate niche-like conditions. SUMMARY: Despite considerable progress in defining the molecular events driving derivation of hematopoietic progenitor cells from PSCs, the generation of robust transplantable HSCs from PSCs remains elusive. We propose that this goal can be facilitated by better understanding of the regulatory pathways governing HSC identity, development of HSC supportive conditions, and examining the marrow homing properties of PSC-derived HSCs.
Authors: Alois Gratwohl; Helen Baldomero; Mahmoud Aljurf; Marcelo C Pasquini; Luis Fernando Bouzas; Ayami Yoshimi; Jeff Szer; Jeff Lipton; Alvin Schwendener; Michael Gratwohl; Karl Frauendorfer; Dietger Niederwieser; Mary Horowitz; Yoshihisa Kodera Journal: JAMA Date: 2010-04-28 Impact factor: 56.272
Authors: Anthony E Boitano; Jian Wang; Russell Romeo; Laure C Bouchez; Albert E Parker; Sue E Sutton; John R Walker; Colin A Flaveny; Gary H Perdew; Michael S Denison; Peter G Schultz; Michael P Cooke Journal: Science Date: 2010-08-05 Impact factor: 47.728
Authors: J M Pantin; R F Hoyt; O Aras; N Sato; M Y Chen; T Hunt; R Clevenger; P Eclarinal; S Adler; P Choyke; R W Childs Journal: Am J Transplant Date: 2015-02-05 Impact factor: 8.086
Authors: Giovanni Amabile; Robert S Welner; Cesar Nombela-Arrieta; Anna Morena D'Alise; Annalisa Di Ruscio; Alexander K Ebralidze; Yevgenya Kraytsberg; Min Ye; Olivier Kocher; Donna S Neuberg; Konstantin Khrapko; Leslie E Silberstein; Daniel G Tenen Journal: Blood Date: 2012-12-04 Impact factor: 22.113
Authors: Trista E North; Wolfram Goessling; Marian Peeters; Pulin Li; Craig Ceol; Allegra M Lord; Gerhard J Weber; James Harris; Claire C Cutting; Paul Huang; Elaine Dzierzak; Leonard I Zon Journal: Cell Date: 2009-05-15 Impact factor: 41.582
Authors: Christopher M Sturgeon; Andrea Ditadi; Geneve Awong; Marion Kennedy; Gordon Keller Journal: Nat Biotechnol Date: 2014-05-18 Impact factor: 54.908
Authors: Jungmin Lee; Brad Dykstra; Joel A Spencer; Laurie L Kenney; Dale L Greiner; Leonard D Shultz; Michael A Brehm; Charles P Lin; Robert Sackstein; Derrick J Rossi Journal: J Clin Invest Date: 2017-05-08 Impact factor: 14.808
Authors: Kai-Hsin Chang; Sarah E Smith; Timothy Sullivan; Kai Chen; Qianhe Zhou; Jason A West; Mei Liu; Yingchun Liu; Benjamin F Vieira; Chao Sun; Vu P Hong; Mingxuan Zhang; Xiao Yang; Andreas Reik; Fyodor D Urnov; Edward J Rebar; Michael C Holmes; Olivier Danos; Haiyan Jiang; Siyuan Tan Journal: Mol Ther Methods Clin Dev Date: 2017-01-11 Impact factor: 6.698