title: Hematopoietic stem cell engineering at a crossroads.
abstract: The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.
authors.affiliation: Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rivière
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
mesh_terms: D060846:Cell Engineering / Q000379:methods*; D018390:Gene Targeting / Q000379:methods / Q000639:trends; D018014:Gene Transfer Techniques; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000302:isolation & purification; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000706:statistics & numerical data; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D012190:Retroviridae / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology
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