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Thrombopoietin requires additional megakaryocyte-active cytokines for optimal ex vivo expansion of megakaryocyte precursor cells. Paper-1456294. The addition of Flt-3 ligand (FL) increases CD41+ cell expansion to approximately 380-fold over input levels.
TPO clearly affects terminal differentiation and the development of (some) high-ploidy human megakaryocytes. Paper-1456294.
However, by itself, TPO is neither necessary nor sufficient to generate a full proliferative/maturational in vitro response within the megakaryocyte compartment. Paper-1456294.
Little is known concerning the interaction of thrombopoietin ( TPO) with other megakaryocyte-active cytokines in directing the early events of megakaryocyte development. Paper-1456294.
We conclude that early proliferative events in megakaryocyte development in vitro are regulated by multiple cytokines, and that TPO markedly affects these early developmental steps. Paper-1456294.
Addition of TPO to IL-1, -6, -11, S generates a biphasic proliferation of CD41(+) cells, accelerates their rate of production, and results in an ex vivo expansion of more than 200-fold. Paper-1456294.
However, its limited in vitro actions on human cell polyploidization suggest that additional megakaryocyte-active cytokines or other signals are essential for the maximal development of human megakaryocytes.
In the absence of TPO, approximately 95% of the expanded cells show the phenotype of promegakaryoblasts; TPO and/or FL addition increases CD41 antigen density and ploidy in a subpopulation of promegakaryoblasts. Paper-1456294.
A moderate (approximately sevenfold) expansion of megakaryocyte progenitor cells (colony-forming unit-megakaryocyte) occurs in the presence of IL-1, -6, -11, S, and the addition of TPO to this cocktail yields an approximately 17-fold expansion. Paper-1456294.
Culture of CD34(+) cells in interleukins (IL) -1, -6, -11, plus stem cell factor (SCF; S) results in a 10- to 12-fold expansion in total cell numbers, whereas total CD41(+) megakaryocytes are expanded approximately 120-fold over input levels. Paper-1456294.
Important links !
iHOP - Information Hyperlinked over Proteins .
Concept & Implementation by Robert Hoffmann.