Generation of a functional and durable vascular niche by the adenoviral
            <i>E4ORF1</i>
            gene

Seandel, Marco; Butler, Jason M.; Kobayashi, Hideki; Hooper, Andrea T.; White, Ian; Zhang, Fan; Vertes, Eva; Kobayashi, Mariko; Zhang, Yan; Shmelkov, Sergey V.; Hackett, Neil R.; Rabbany, Sina Y.; Boyer, Julie L.; Rafii, Shahin

doi:10.1073/pnas.0805980105

Cited by 128 publications

(159 citation statements)

References 12 publications

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“…These investigators also suggested that leukemic cell-induced upregulation of VEGFR2 signaling in E4ORF1 ECs led to the elaboration of angiocrine factors that promoted leukemic cell growth. 19,98 Taken together, these studies suggest that leukemic cells elaborate growth factors, which augment EC proliferation, and ECs symbiotically mediate the proliferation and survival of leukemic cells. 19,92,[96][97][98] In addition to the contribution of the BM vascular niche and other niche cells to leukemic cell growth, BM-derived ECs and stromal cells also regulate the establishment of metastatic niches for solid tumor cells.…”

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 99%

“…19,98 Taken together, these studies suggest that leukemic cells elaborate growth factors, which augment EC proliferation, and ECs symbiotically mediate the proliferation and survival of leukemic cells. 19,92,[96][97][98] In addition to the contribution of the BM vascular niche and other niche cells to leukemic cell growth, BM-derived ECs and stromal cells also regulate the establishment of metastatic niches for solid tumor cells. 59,99,100 Lyden et al 101 showed that blockade of recruitment of BM ECs and BM HPCs to metastatic sites impairs tumor angiogenesis and cancer growth in vivo.…”

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 99%

“…96 Similarly, culture of primary AML cells with lung or dermal ECs promotes EC proliferation in vitro. 97 Seandel et al 98 showed that contact culture of HL60 cells with an E4ORF1 EC cell line also supports the expansion of HL60 cells in culture. These investigators also suggested that leukemic cell-induced upregulation of VEGFR2 signaling in E4ORF1 ECs led to the elaboration of angiocrine factors that promoted leukemic cell growth.…”

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 99%

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The vascular niche: home for normal and malignant hematopoietic stem cells

2011

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Hematopoietic stem cells (HSCs) are uniquely capable of selfrenewal and provision of all of the mature elements of the blood and immune system throughout the lifetime of an individual. HSC self-renewal is regulated by both intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments or 'niches' wherein HSCs reside. HSCs have been shown to reside in close association with bone marrow (BM) osteoblasts in the endosteal niche and also in proximity to BM sinusoidal vessels. An unresolved question surrounds whether the endosteal and vascular niches provide synchronous or redundant regulation of HSC fate or whether these niches provide wholly unique regulatory functions. Furthermore, while some aspects of the mechanisms through which osteoblasts regulate HSC fate have been defined, the mechanisms through which the vascular niche regulates HSC fate remain obscure. Here, we summarize the anatomic and functional basis supporting the concept of an HSC vascular niche as well as the precise function of endothelial cells, perivascular cells and stromal cells within the niche in regulating HSC fate. Lastly, we will highlight the role of the vascular niche in regulating leukemic stem cell fate in vivo. Leukemia (2012) Concept of the hematopoietic stem cell (HSC) nicheThe concept of an instructive role for the bone marrow (BM) microenvironment in regulating hematopoietic cell fate was introduced at least 50 years ago and has been validated over the past decade. 1-9 It has long been postulated that HSCs reside in specialized niches within the adult BM. [8][9][10][11][12][13][14] In addition to HSCs and their progeny, the BM comprises a rich network of osteoblasts, mesenchymal stem cells (MSCs), neuronal cells, adipocytes, sinusoidal vessels and perivascular reticular cells (Figure 1). Recently, genetic knockout studies have begun to demonstrate the functional role of specific cells within the BM microenvironment in regulating hematopoiesis. [3][4][5]7,[15][16][17][18][19][20] Interestingly, certain niches within the BM may uniquely regulate HSC homeostasis in vivo while other niches may be more relevant to HSC regeneration following injury. However, it remains unknown whether there is meaningful 'cross-talk' between distinct microenvironmental cells in regulating HSC fate in vivo. Interestingly, as early as 1961, Fliedner et al. 9 postulated that the recovery of hematopoiesis in rats following 1000 cGy total body irradiation (TBI) required the recovery of an intact vasculature. Similarly, McClugage et al. 14 used a window chamber to visualize dynamic changes in tibial BM cellularity and architecture in live rabbits. Interestingly, both studies suggested a strong association between vasculogenesis in the BM and the hematopoietic response to stress or injury. 9,14 Role of the BM osteoblast With advances in mouse genetics and microscopy, the function of the BM osteoblast in regulating hematopoiesis and HSC homeostasis has been demonstrated. 4,5,14,[21][22][23][24] Human osteoblasts were shown by Taichma...

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Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 99%

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 99%

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 99%

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The vascular niche: home for normal and malignant hematopoietic stem cells

2011

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“…E4 þ ECs were obtained as previously described (22). Briefly, isolated HUVECs were transduced with the early 4 region (E4) of the adenoviral vectors (AdE4 þ ) to generate durable PEC feeders.…”

Section: Cell Culturementioning

confidence: 99%

“…We demonstrated that the cross-talk between ovarian cancer cells (OCC) and established human umbilical vein endothelial cell line (HUVEC) resulted in an activation of Akt pathway among others. To model tumor endothelium, we used the Akt-activated endothelial cells (E4 þ ECs) to study the involvement of the endothelial component in the resistance to antiangiogenic therapy (22). We demonstrated that in the setting of tumor-endothelial cross-talk, endothelial cell activation of PI3K/Akt pathway induces an autocrine loop through the proangiogenic factor FGF2, bypassing the VEGFR pathway.…”

Section: Introductionmentioning

confidence: 99%

Akt-Activated Endothelium Constitutes the Niche for Residual Disease and Resistance to Bevacizumab in Ovarian Cancer

Guerrouahen

Pasquier

Kaoud

et al. 2014

Molecular Cancer Therapeutics

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Generating human hematopoietic stem cells in vitro –exploring endothelial to hematopoietic transition as a portal for stemness acquisition

Slukvin

2016

FEBS Letters

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Advances in cellular reprogramming technologies have created alternative platforms for the production of blood cells, either through inducing pluripotency in somatic cells or by way of direct conversion of non-hematopoietic cells into blood cells. However, de novo generation of hematopoietic stem cells (HSCs) with robust and sustained multilineage engraftment potential remains a significant challenge. Hemogenic endothelium (HE) has been recognized as a unique transitional stage of blood development from mesoderm at which HSCs arise in certain embryonic locations. The major aim of this review is to summarize historical perspectives and recent advances in the investigation of endothelial-hematopoietic transition (EHT) and HSC formation in the context of aiding in vitro approaches to instruct HSC fate from human pluripotent stem cells. In addition, direct conversion of somatic cells to blood and HSCs and progression of this conversion through HE stage are discussed. A thorough understanding of the intrinsic and microenvironmental regulators of EHT that lead to the acquisition of self-renewal potential by emerging blood cells, is essential to advance the technologies for HSC production and expansion.

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Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene

Abstract: angiogenesis ͉ endothelium ͉ adenovirus ͉ tumor ͉ stem

Cited by 128 publications

References 12 publications

The vascular niche: home for normal and malignant hematopoietic stem cells

The vascular niche: home for normal and malignant hematopoietic stem cells

Akt-Activated Endothelium Constitutes the Niche for Residual Disease and Resistance to Bevacizumab in Ovarian Cancer

Generating human hematopoietic stem cells in vitro –exploring endothelial to hematopoietic transition as a portal for stemness acquisition

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