Ex vivo HSC expansion challenges the paradigm of unidirectional human hematopoiesis

• Published in: Annals of the New York Academy of Sciences Vol. 1466; no. 1; pp. 39 - 50
• Main Authors: Papa, Luena, Djedaini, Mansour, Hoffman, Ronald
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2020; John Wiley and Sons Inc
• Subjects: Biological Sciences; BM niches; Bone marrow; Cell Biology; Cell self-renewal; ex vivo expansion; Expansion; Hematopoiesis; Hematopoietic stem cells; HSCs; Immunology; Mitochondria; mitochondrial network; Molecular Biology; Plastic foam; Review; Reviews; Stem cells; Transcription; BM niches; HSCs; mitochondrial network; ex vivo expansion
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.14133

Understanding mechanisms that determine the behavior of human hematopoietic stem cells (HSCs) is essential for developing novel strategies to expand ex vivo the number of fully functional HSCs. In this review, we focus on the complex interplay between intrinsic mechanisms regulated by transcriptional and mitochondrial networks and extrinsic signals imposed by the bone marrow microenvironment, which in concert regulate the balance between HSC self‐renewal and differentiation. Such integrated signaling mechanisms that dictate the fate of HSCs in vivo must be recapitulated ex vivo to achieve successful expansion of clinically relevant HSCs. We also highlight some of the most recent ex vivo HSC expansion strategies that have currently entered clinical development. Finally, based on the evidence reviewed here and lessons learned from ex vivo HSC expansion, we raise some critical questions regarding HSC fate and the cellular plasticity of hematopoietic cells that challenge the unidirectional model of human hematopoiesis. In this review, we focus on the complex interplay between intrinsic mechanisms regulated by transcriptional and mitochondrial networks and extrinsic signals imposed by the bone marrow microenvironment, which in concert regulate the balance between HSC self‐renewal and differentiation. We also highlight some of the most recent ex vivo HSC expansion strategies that have currently entered clinical development and raise some critical questions regarding HSC fate and the cellular plasticity of hematopoietic cells that challenge the unidirectional model of human hematopoiesis.