Hematopoietic stem cells: to be or Notch to be

Bigas, Anna; Espinosa, Lluís

doi:10.1182/blood-2011-10-355826

Cited by 118 publications

(99 citation statements)

References 147 publications

(138 reference statements)

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“…NAM-mediated expansion resulted to a median 82-fold increase in the CD34 þ cell dose. Neutrophil engraftment was robust at a median time of 10 days (range [7][8][9][10][11][12][13][14] and durable with no increased toxicity. There were no graft failures and long-term engraftment was obtained from the expanded unit (authors' personal communications).…”

Section: Cord Blood Graft Enhancement M Norkin Et Almentioning

confidence: 96%

“…The Notch signaling pathway has an important regulatory role in the expansion and differentiation of human HPC. 10 Preclinical data have shown the ability of engineered Notch ligands to influence HPC differentiation. Incubation of murine marrow precursors in the presence of Notch ligand and stimulatory cytokines, such as SCF, IL-6, IL-11, Flt3-l, IL-7 and GM-CSF, resulted in a several-log increase in the number of hematopoietic precursors, which were capable of differentiating into mature lymphoid and myeloid cells.…”

Section: Cord Blood Graft Enhancement M Norkin Et Almentioning

confidence: 99%

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Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic?

Norkin

Lazarus

Wingard

2012

Bone Marrow Transplant

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Umbilical cord blood (UCB) is an attractive stem cell graft option for patients who need allogeneic hematopoietic stem cell support, but lack a suitable HLA-matched donor. However, the limited number of hematopoietic progenitor cells in a single cord blood unit can lead to an increased risk of graft failure, delayed hematological recovery and prolonged immunosuppression, particularly in adult patients. Several strategies to overcome these potential limitations are being evaluated. In this review, we discuss promising ex vivo manipulations to enhance cord blood engraftment capacity such as culture of UCB cells with stimulatory cytokines and growth factors, mesenchymal cells, Notch ligand, copper chelators, prostaglandins, complement components, nicotinamide and CD26/DPPIV inhibitors. All these approaches are now in early clinical trials. However, despite the fact that several cord blood enhancement strategies have resulted in increased numbers of progenitor cells and faster neutrophil recovery, the ability of these techniques to significantly shorten engraftment time and permit the use of cord units with low numbers of total nucleated cells, or accomplish reliable engraftment with a single cord, have yet to be convincingly demonstrated. The ultimate clinical value of ex vivo cord blood expansion or manipulation has not been defined yet, and the current data do not permit predicting which technology will prove to be the optimal strategy. Nevertheless, expectations remain high that eventually ex vivo enhancement will be able to improve clinical outcomes and significantly extend the applicability of UCB transplantation.

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Section: Cord Blood Graft Enhancement M Norkin Et Almentioning

confidence: 96%

Section: Cord Blood Graft Enhancement M Norkin Et Almentioning

confidence: 99%

Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic?

Norkin

Lazarus

Wingard

2012

Bone Marrow Transplant

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“…However, although Notch stimulates HSCs reconstitution after damage in the mice, it remains unclear if the canonical Notch-pathway contributes to homeostatic maintenance of the HSCs [173,226,[231][232][233]. Expression of Notch-receptors at early stages of the hematopoiesis is, probably, involved in the choice of differentiation pathway and can be used for identification of specific progenitor cells with predestined fate [233].…”

Section: Notchmentioning

confidence: 99%

“…Notch-signaling plays an important role in many processes of the embryonic and postnatal development and regulates the fate of various populations of adult stem cells [222,226]. Notch favors HSCs self-maintenance.…”

Section: Notchmentioning

confidence: 99%

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Nikolskaya¹,

Butenko²

2016

JCOT

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This article focuses on (1) the analysis of the structural-functional organization of bone marrow niches of the hematopoietic stem cells, (2) the role of the intercellular contact interactions and humoral regulation factors in these niches, in particular CXCL12, SCF and TGFβ,and (3) KEYWORDS: bone marrow, hematopoietic stem cell niche, multipotent stromal cells, hematopoiesisMaksimov and finally established at the end of the past century, it is not only the number but also entire known diversity of cell elements of immune and blood systems originate from only one type of the progenitor elements -the HSCs (unitary theory) [2].Life force and productivity of the HSCs is proved, for example, by the fact that 99.9 % of all blood-generating cells, HSCs included, in the irradiated mice can perish, and the surviving stem cells rapidly renew blood formation, including proper population as well as all types of the committed progenitors [3]. Along same sequence, the fact of non-exhaustion of blood formation after repeated damaging exposures is explained by the presence and functioning of the HSCs [1].The specialized cells of adult and fetal periods of ontogenesis, residing in the bone marrow (BM) in the quiescent state and capable, together with blood-forming microenvironment, to realize underlying programs for self-maintenance and multipotency allowing them (with maintained amount of HSCs) to release necessary amount of cells into differentiation along various directions that ultimately leads to the formation of all forms of blood elements, including immune system cells. It should be noted that the self-maintenance is not identical to the immortality. Stem cells are characterized by sufficiently long life, commensurable with entire organism's life course. Several genetic regulatory programs have been established which are of great importance in the process of HSCs self-maintenance. It is also known that stem cells in various tissues are controlled by common genetic programs maintaining their nature [4,5].It is theorized that stem cells are the clonogenic units which under certain conditions can be increased in their number at the expense Immune system is the structural-functional and interrelated commonness of the hematopoietic and stromal cells. Different in their origin, structure and functions, the populations and subpopulations of lymphoid and myeloid cells make a complete wholeness in the definite tissues and organs where they closely cooperate with non-hematopoietic elements. Constant and strictly regulated intensity of hematopoiesis with production of various cell types is also conditioned and controlled by cooperation of the hematopoietic and stromal cells. Timely repopulation of the immune system with hematopoietic cells-precursors, lymphocytes, leucocytes and stromal cells, newly maturing in the bone marrow, is the main condition for effective immune system functioning. The number of cells formed per time unit is plentiful. According to the given data, nearly 10 11 neutrophils (about 100 g of mass) per...

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“…[61,62] HSCs are capable to differentiate into all blood lineages and can regenerate bone marrow after loss. [60,63,64] MSCs can differentiate into various cellular phenotypes according to the tissue they migrate, e.g. chondrocytes if they move to cartilage tissue, osteoblasts if in bone, myoblasts if in muscle.…”

Section: Natural Tissue Regenerationmentioning

confidence: 99%

Instructive composites for bone regeneration

Barbieri¹

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Hematopoietic stem cells: to be or Notch to be

Cited by 118 publications

References 147 publications

Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic?

Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic?

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Instructive composites for bone regeneration

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