Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids

Jaźwiec, Bożena; Solanilla, A.; Grosset, Christophe; Fx, Mahon; Dupouy, Maryse; Pigeonnier-Lagarde, V.; Belloc, Françis; Schweitzer, Karin; Reiffers, Josy; Ripoche, Jean

doi:10.1038/sj.leu.2401086

Cited by 33 publications

(37 citation statements)

References 58 publications

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“…In vitro and in vivo studies have also clearly demonstrated that ECs regulate the self-renewal and regeneration of adult HSCs (Table 1). 16,18,19,[40][41][42]45,52,53,55,[104][105][106] Although mechanistic pathways such as Notch and CXCR4-SDF1 signaling have been shown to contribute to BM endosteal and reticular cell regulation of HSC fate in vivo, 4,7 the mechanisms through which BM ECs regulate HSC maintenance and regeneration remain less well defined. 3 In parallel, phenotypic and functional characterization of LSCs has been demonstrated, coupled with the demonstration of homing and engraftment of LSCs in vascular niches in vivo.…”

Section: Ongoing Questions and Opportunitiesmentioning

confidence: 99%

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: Ongoing Questions and Opportunitiesmentioning

confidence: 99%

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

2011

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“…61 These preclinical studies identify further UCB graft engineering questions including the role of accessory lymphoid populations in ex vivo expanded allogeneic grafts, [62][63][64][65][66] as well as the role of stromal elements in maintaining immature stem cells with self-renewal capacity during expansion. [67][68][69][70] In summary, banked unrelated umbilical cord blood (UCB) has emerged as a substitute allogeneic stem cell source, due to the lack of available HLA-matched related donors for patients requiring allogeneic transplantation, and the observed increased incidence and severity of acute and chronic GVHD when alternative HLA-matched unrelated or partially mismatched family member grafts are utilized. Early clinical reports of UCB transplantation have focused primarily on pediatric or small stature adult recipients.…”

Section: Future Initiatives: Ucb Transplantationmentioning

confidence: 99%

Umbilical cord blood for allogeneic transplantation in children and adults

Laughlin

2001

Bone Marrow Transplant

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Summary:Early clinical reports outlining outcomes for primarily pediatric patients undergoing UCB transplantation, point to delayed time to hematopoietic recovery, and favorable incidence and severity of graft-versus-host disease. Intensive clinical and laboratory research is ongoing focused on strategies to foster UCB allogeneic donor engraftment, thereby allowing wider application of this stem cell source for patients requiring allogeneic transplantation. Bone Marrow Transplantation (2001) 27, 1-6. Keywords: umbilical cord blood; allogeneic transplantation Allogeneic blood and bone marrow stem cell transplantation is limited by the availability of suitable HLAmatched related donors. In 1988, umbilical cord blood (UCB) hematopoietic stem cells (HSC) from a related sibling were transplanted successfully into a child with Fanconi anemia. 1 Subsequently, UCB from HLA-mismatched related 2 and unrelated donors has been shown to successfully engraft pediatric 3-8 and a few reported adult patients 6,9-11 with hematologic malignancies, immunodeficiency syndromes, inborn errors of metabolism, or marrow failure syndromes. This article will review the use of UCB as a suitable alternative for allogeneic transplantation. Tables 1 and 2 outline the advantages and disadvantages for the application of UCB as a new source of HSC for patients requiring allogeneic transplantation. UCB collection and bankingSince the first successful unrelated UCB transplant was performed by J Kurtzberg and the pediatric transplant team at Duke University in 1993, 7 clinical and laboratory studies have burgeoned and standard operating procedures have been developed for the collection, processing, and storage of UCB units. [12][13][14][15][16][17][18][19] UCB collection is performed during the final phase of labor or, more commonly, after delivery of

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“…Breems et al (14) reported that the expansion of CD34 ϩ cells from mobilized PB stem cells was enhanced by the noncontact and contact cultures with HBMSC, with a better graft quality in the latter. HBMSC and HUVEC secrete a panel of early promoting cytokines and chemokines, including TPO, FL, SCF, PDGF, and SDF-1 (24)(25)(26). HBMSC and HUVEC were also shown to express hDelta-1, hDelta-4, Notch-1, Notch-2, and Kuzbanian, the metalloprotease responsible for cleavage of Delta ligands (27).…”

Section: Discussionmentioning

confidence: 99%

Platelet-Derived Growth Factor Enhances Expansion of Umbilical Cord Blood CD34+ Cells in Contact with Hematopoietic Stroma

Zhang

et al. 2005

Stem Cells and Development

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Stem cell expansion remains an elusive but highly desirable goal. Here we show that platelet-derived growth factor (PDGF), along with cultured endothelial or stromal cells, significantly enhances expansion of human CD34+ cells in vitro. In media supplemented with thrombopoietin, stem cell factor, flt-3 ligand, and granulocyte-colony stimulating factor, CD34+ cells, as well as CFU-GM, BFU-CFU-E, CFU-GEMM, and CFU-MK, increased by 34.3-, 138-, 59.7-, 38.4-, and 86.0-fold, respectively. Co-culturing of CD34+ cells with cultured stromal cells or human umbilical cord vein endothelial cells (HUVECs) greatly enhanced expansion efficiency. The presence of PDGF (50 ng/ml) further augmented expansion, such that increases of 77.0-, 262-, 90.0-, 93.0-, and 200-fold, respectively, were achieved. Six weeks after infusion of expanded cells into NOD/SCID mice, human CD45+ cells were detected in recipients' bone marrow, spleen, and peripheral blood. Our results provide a rationale for development of a stem cell expansion protocol for clinical applications.

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Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids

Cited by 33 publications

References 58 publications

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

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

Umbilical cord blood for allogeneic transplantation in children and adults

Platelet-Derived Growth Factor Enhances Expansion of Umbilical Cord Blood CD34+ Cells in Contact with Hematopoietic Stroma

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