A New View of Stem Cell Dynamics
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Purpose of Review
Our understanding of the biology of hematopoietic stem cells is evolving beyond hierarchical models and markers of stem cell purification to a far more fluid model wherein degrees of multipotency of individual cells can change over time. This review is to outline these new concepts:
The long-term repopulating hematopoietic stem cell is a proliferating cell, which is continually changing in phenotype. It cannot be purified by current surface epitope techniques. The cycling nature of the cell has been established by three separate approaches; separation of whole marrow into G0/G1 and S/G2/M fractions followed by evaluation of long-term in vivo repopulation in irradiated mice, tritiated thymidine suicide of marrow cells with repopulation assays, and in vivo BrdU studies to estimate flux through cycle. Other work has suggested that stem cell studies need to be considered within the context of transplant-based or normal baseline hematopoiesis; they are quite distinct and likely have differential influences governing stem cell self-renewal and differentiation. Hematopoietic stem cell functions are further modulated by interactions with a variety of extracellular vesicles and influenced by circadian rhythms and other variables.
The true nature of the system remains to be defined, and such definition will elucidate the basic nature of stem cell biology and indicate specifics of clinical relevance.
KeywordsHematopoietic stem cells Cell cycle Extracellular vesicles Hematopoiesis
Compliance with Ethical Standards
Conflict of Interest
P. Quesenberry, S. Wen, M. Dooner, and L. Goldberg declare that they have no conflict of interest.
G. Camussi has a patent EP2604271B1, US8,568,771B2 issued.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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