Thrombopoietin Enhances Generation of CD34+ Cells from Human Embryonic Stem Cells

Srivastava, Anand; Nedelcu, Elena; Esmaeli-Azad, Babak; Mishra, Rangnath; Carrier, Ewa

doi:10.1634/stemcells.2006-0701

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…Prior studies have demonstrated that addition of TPO increases formation of primitive hematopoietic progenitors in primate EB differentiation models [39]. It was also shown that TPO and VEGF induce early hematopoietic differentiation of EB-derived human ES cells [40]. Our data show that inclusion of both VEGF and TPO in the medium enhances hematopoietic differentiation, as evidenced not only by up-regulated expression of CD34 and SCL, but also by increased numbers of CFCs at day 14.…”

Section: Discussionsupporting

confidence: 69%

Mesoderm is committed to hemato-endothelial and cardiac lineages in human embryoid bodies by sequential exposure to cytokines

Zhu

Jin-yuan

Chen

2013

Experimental Cell Research

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Section: Discussionsupporting

confidence: 69%

Mesoderm is committed to hemato-endothelial and cardiac lineages in human embryoid bodies by sequential exposure to cytokines

Zhu

Jin-yuan

Chen

2013

Experimental Cell Research

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“…Because it is well known that signaling mediated by the TPO/c-Mpl axis is indispensable for megakaryopoiesis, 24,25 we suggest that augmented expression of c-Mpl mediated via a VEGF signaling pathway increases megakaryopoiesis and thrombopoiesis to levels not seen in the absence of VEGF ( Figure 3A,B), which is consistent with a recent report. 26 Because the cells making up ES-sacs manifest characteristics similar to those of endothelial cells (Figure 2A,B), and because bFGF and PlGF, like VEGF, are necessary for endothelial cell growth, [27][28][29] we next assessed the respective capacities of bFGF or PlGF to promote the generation of ES-sacs and hematopoietic progenitors. Interestingly, bFGF at concentrations of 2.5 or 10 ng/mL exerted a dose-dependent inhibitory effect, while PlGF at 50 ng/mL tended to increase the generation of ES-sacs ( Figure 3C) and platelets (data not shown).…”

Section: Org Frommentioning

confidence: 99%

Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors

Takayama

Nishikii

Usui

et al. 2008

Blood

293

285

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Human embryonic stem cells (hESCs) could potentially represent an alternative source for blood transfusion therapies and a promising tool for studying the ontogeny of hematopoiesis. When we cultured hESCs on either C3H10T1/2 or OP-9 cells to facilitate hematopoiesis, we found that exogenous administration of vascular endothelial growth factor promoted the emergence of sac-like structures, which we named embryonic stem cellderived sacs (ES-sacs). These ES-sacs consisted of multiple cysts demarcated by cellular monolayers that retained some of the properties of endothelial cells. The spherical cells inside ES-sacs expressed primarily CD34, along with VE-cadherin, CD31, CD41a, and CD45, and were able to form hematopoietic colonies in semisolid culture and to differentiate into mature megakaryocytes by day 24 in the presence of thrombopoietin. Apparently, ESsacs provide a suitable environment for hematopoietic progenitors. Relatively large numbers of mature megakaryocytes could be induced from the hematopoietic progenitors within ES-sacs, which were then able to release platelets that displayed integrin ␣IIb␤3 activation and spreading in response to ADP or thrombin. This novel protocol thus provides a means of generating platelets from hESCs, which could serve as the basis for efficient production of platelets for clinical transfusion and studies of thrombopoiesis. (Blood. 2008;111:5298-5306)

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“…In a series of manuscripts Bhatia's group has established serum-based cultivation conditions with mesoderm/hematopoietic cell-inducing cytokines (BMP-4, VEGF 165 , IL-3, IL-6, SCF, FLT-3L, and G-CSF) that lead to a high of blood cells in culture [144][145][146][147][148][149]. Similarly, we have shown that TPO and VEGF induce generation of CD34+ cells form human ES cells [150]. Other groups have also studied the expansion of lympho-myeloid hematopoietic tissue from hES cells via different culture methodologies [148; 149; 151-154].…”

Section: Recent Progress With Human Es Cells (Hes): Blood From Human mentioning

confidence: 83%

Prospects of Embryonic Stem Cells in Treatment of Hematopoietic Disorders

Srivastava

Malhotra²,

Esmaeli-Azad³

et al. 2007

CPB

Self Cite

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Cellular therapies derived from embryonic stem (ES) cells have gained a renewed interest with the experimental demonstration that an embryonic stem cell lines can be established from human blastocyst-stage embryos and prompted to differentiate into almost all types of cells present in the body including hematopoietic cells. Hematopoiesis is a series of cellular processes whereby short-lived mature blood cells are continuously replenished from a pool of rare pluripotential hematopoietic stem cells, in a highly orchestrated process. Aberrances in this intricate process may lead to a malignancy of essential blood-forming organs, causing diseases such as leukemia, aplastic anemia, lymphoma, myelodysplasia and myeloproliferative disorders. Embryonic stem cells show great potential and it may be technologically feasible to transplant differentiated ES cells and to cure various kinds of blood disorders. Understanding the biology of ES cell derived hematopoiesis may lead to the development of co-transplantation protocols that will result in a decreased morbidity and mortality by providing safer and simpler transplantation procedures for patients with malignant and non-malignant conditions. The potential utility of ES cells for gene therapy, tissue engineering and the treatment of a wide variety of currently untreatable diseases is simply too essential to ignore, however, our knowledge and ability to deliver these forms of therapy in a safe and efficient manner requires additional advances in the understanding of the basic biology of ES cells. In this article, we will discuss the factors and methodologies responsible for the differentiation of ES cells into hematopoietic progenitors and their potential to treat different blood related diseases.

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Thrombopoietin Enhances Generation of CD34+ Cells from Human Embryonic Stem Cells

Abstract: ABSTRACT

Cited by 18 publications

References 28 publications

Mesoderm is committed to hemato-endothelial and cardiac lineages in human embryoid bodies by sequential exposure to cytokines

Mesoderm is committed to hemato-endothelial and cardiac lineages in human embryoid bodies by sequential exposure to cytokines

Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors

Prospects of Embryonic Stem Cells in Treatment of Hematopoietic Disorders

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