Engineering Hematopoietic Stem Cells: Lessons from Development

• Published in: Cell stem cell Vol. 18; no. 6; pp. 707 - 720
• Main Authors: Rowe, R. Grant, Mandelbaum, Joseph, Zon, Leonard I., Daley, George Q.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.06.2016
• Subjects: Animals; Cell Engineering - methods; Danio rerio; Embryonic Development; Hematopoiesis; Hematopoietic Stem Cells - cytology; Humans; Models, Biological; Time Factors
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2016.05.016

Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy. Rowe et al. consider the current strategies aimed at engineering hematopoietic stem cells in vitro. They discuss the role of conserved developmental timing processes in vertebrate hematopoiesis and highlight how identification and manipulation of stage-specific factors that specify HSC developmental state may be harnessed to engineer HSCs for therapy.