title: Cell cycle regulation in human hematopoietic stem cells: from isolation to activation.
abstract: Hematopoietic stem cells (HSCs) reside mostly in the bone marrow and are defined by their ability to self-renew and to give rise by proliferation and differentiation to all blood lineages. Despite this strict definition HSCs cannot be unequivocally identified in the hematopoietic cell pool. Despite innumerable studies over the years, which focused on the search of the ideal phenotypic marker to selectively isolate stem cells, most of the known markers still define heterogeneous populations in different stages of commitment. Functional features attributed to stem cells have also been investigated, and among these the use of fluorescent markers which allow tracking of the cell division record of each cell. A second issue, after the initial isolation process, is the expansion ex vivo in order to obtain production of large numbers of homogeneous cell populations for both biological studies and clinical applications. Expansion ex vivo is difficult to modulate and normally occurs only along with commitment and consequent loss of multipotentiality. Moreover expansion obtained ex vivo is significantly reduced to that achievable in vivo. One of the key features of HSCs is a very slow proliferation rate, but when the appropriate stimuli are delivered, the proliferation rate can drastically increase. In normal physiological conditions a strict balance is maintained between the number of cells that maintain the original pool and those that proliferate and differentiate. Numerous data in recent years are providing some clue to elucidate the key steps in this tightly controlled process, but the dynamics that regulate which and how many cells self-renew to maintain the pool, and which proliferate and become committed to give rise to the mature blood elements, are still unclear.
authors: Department of Gynecology, Catholic University, Rome, Italy. maria.marone@tiscalinet.it
authors: Maria
authors: M
authors: Marone
authors: Daniela
authors: D
authors: De Ritis
authors: Giuseppina
authors: G
authors: Bonanno
authors: Simona
authors: S
authors: Mozzetti
authors: Sergio
authors: S
authors: Rutella
authors: Giovanni
authors: G
authors: Scambia
authors: Luca
authors: L
authors: Pierelli
mesh_terms: D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008954:Models, Biological
chemical_list: D018797:Cell Cycle Proteins; D016207:Cytokines