Stem cell factor induces HIF-1α at normoxia in hematopoietic cells

Pedersen, Malin; Löfstedt, Tobias; Sun, Jianmin; Mengelbier, Linda Holmquist; Påhlman, Sven; Rönnstrand, Lars

doi:10.1016/j.bbrc.2008.09.102

Cited by 67 publications

(54 citation statements)

References 23 publications

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“…Cell biological studies using HS(P)Cs indicated that their functions as well as their quiescence state are maintained most effectively under hypoxic conditions (10,(47)(48)(49)(50)(51)(52). Hypoxia stabilizes the HIF-1␣ protein, a master regulator of oxygen homeostasis, and activates HIF-1␣-mediated signals in HSCs (48,53,54). Furthermore, leukocyte adhesion to activated endothelial cells was shown to be HIF-1␣-dependent (32).…”

Section: Discussionmentioning

confidence: 99%

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

Nishii

Nakaseko

Jiang

et al. 2013

Journal of Biological Chemistry

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Background: Serum levels of the soluble LR11 fragment (sLR11) increase in patients with acute leukemia. Results: Hypoxia-induced factor (HIF)-1␣ activation increases LR11 levels, and sLR11 enhances adhesion of HSPCs to BM stromal cells via a uPAR-mediated pathway. Conclusion: sLR11 regulates hypoxia-induced attachment of HSPCs. Significance: sLR11 may stabilize the hematological pool size by controlling HSPC attachment to the BM niche.

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Section: Discussionmentioning

confidence: 99%

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

Nishii

Nakaseko

Jiang

et al. 2013

Journal of Biological Chemistry

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“…30,31 Therefore, the finding that the hypoxic features of HSPCs were not related to specific positioning in BM microdomains did not rule out that local microgradients of pO 2 exist locally in BM regions and may influence HSPC fate. To test this possibility, Spencer et al pioneered the use of 2-photon phosphorescence-based microscopy to detect and measure local extracellular oxygen concentrations in the BM of the skull in live animals, thereby providing for the first time an accurate picture of the topography of oxygen distribution in the BM.…”

Section: Direct In Vivo Measurement Of Oxygen Concentrations In Divermentioning

confidence: 99%

The science behind the hypoxic niche of hematopoietic stem and progenitors

Nombela‐Arrieta

Silberstein

2014

Hematology

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In blood, oxygen is transported principally by hemoglobin tetrameric molecules in erythocytes, which allow for the delivery to tissue cells. When anemia occurs, such as perisurgically or after trauma, blood transfusion is administered to replace the deficit in oxygen-carrying capacity. During embryogenesis and later in adult life, tissue oxygen levels control multiple key cellular functions. Low tissue oxygen levels in particular are physiologically relevant to stem cells by controlling their metabolism and cell fate. In adult life, hematopoietic stem cells reside in specified BM microenvironments/niches, where their quiescence and differentiation are presumably also influenced by cell-intrinsic and cell-extrinsic (niche) factors. Novel imaging technologies have allowed determination of the spatial localization of hematopoietic stem/progenitor cells (HSPCs), as well as the topography of oxygen distribution in BM cavities. Together, these recent advances have contributed to the emergence of a novel model that challenges the previous concept of a hypoxic hematopoietic stem cell niche characterized by poorly perfused endosteal zones with the deepest hypoxia. HSPCs display a hypoxic phenotype despite residing in close association with arterial or sinusoidal vascular networks. The entire BM cavity is hypoxic and unexpectedly exhibits an opposite oxygen gradient to the one initially proposed because arteriole-rich endosteal zones are relatively less hypoxic than deeper regions of the BM perfused by dense sinusoidal networks. Therefore, further studies are warranted to elucidate to what extent differences in oxygen tensions in these diverse microenvironments influence HSPC homeostasis. Learning Objective• To understand the fundamental basic research carried out to investigate the relevance of hypoxic conditions in bone marrow microenvironments that support hematopoietic stem cell maintenance Oxygen in tissues and stem cell biologyDuring evolution, fluctuations in atmospheric oxygen concentration have defined eukaryotic life forms on earth, exemplified by the adoption of efficient oxidative phosphorylation (ie, aerobic metabolism) to support more complex and multicellular organisms. 1

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“…Стимуля ция IGF 1 также приводит к индукции HIF 1α через ERK путь, в то время как гипоксия, выз ванная экспрессией HIF 1α, не зависит от ERK [21]. Однако, высокие уровни экспрессии бел ка HIF 1α, как известно, возникают при стиму ляции стволовыми клетками в условиях нор моксии по Akt и ERK зависимым путям [22].…”

Section: обсуждение результатовunclassified

Transplantation of Genetic Modified Stem Cells Overexpressing Therapeutic Growth Factorsfor the Treatment of Experimental Rat Myocardial Infarction

Konoplyannikov¹,

Haider²,

Ashraf³

2013

Journal of Clinical Practice

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1ÔÃÁÓ Ôåäåðàëüíûé íàó÷íî-êëèíè÷åñêèé öåíòð ñïåöèàëèçèðîâàííûõ âèäîâ ìåäèöèíñêîé ïîìîùè è ìåäèöèíñêèõ òåõíîëîãèé ÔÌÁÀ Ðîññèè, Ìîñêâà 2 Óíèâåðñèòåò Öèíöèííàòè, Îãàéî, ÑØÀ Мы проанализировали гипотезу, что одновременная трансгенная модификация трансплантируемых стволовых клеток 4 мя ростовыми факторами активирует разнообразные сигнальные механизмы для выживания введенных клеток, а также мобилизацию различных стволовых/прогениторных клеток для кардиогенеза при терапии инфаркта миокарда. Плазмиды, несущие гены, кодирующие IGF 1, VEGF, SDF 1α и HGF, были сконструированы и трансфицированы в скелетные миобласты (SM) крыс. Повышенная экспрессия ряда факторов в трансфицированных SM (TransSM) была подтверждена методами ПЦР, Вестерн блоттинга (ВБ) и иммунофлюоресцентного окрашивания. Кондиционная среда от TransSM обладала цитопротекторными свойствами для кардиомиоцитов в условиях окислительного стресса, стимулировала миграцию клеток HUVEC, и усиливала ангиогенез клеток HUVEC in vitro. Интрамиокардиальная трансплантация 1,5×106 TransSM продемонстрировала обширную мобилизацию стволовых/прогениторных клеток в инфарктном миокарде и улучшала интегрирование TransSM в сердце. Экстенсивный неомиогенез и ангиогенез наблюдался через 8 недель после трансплантации. Итак, одновременная активация разнообразных сигнальных механизмов благодаря повышенной экспрессии нескольких ростовых факторов вызывает массовую мобилизацию и хоминг как стволовых/прогениторных клеток из костного мозга и циркулирующих в крови, так и резидентных кардиальных стволовых клеток, что приводит к ускоренной репарации инфарктного миокарда.Ключевые слова: стволовые клетки, инфаркт миокарда, трансгенная модификация, трансплантация клеток, сердечно сосудистая регенерация, паракринные факторы TRANSPLANTATION OF GENETIC MODIFIED STEM CELLS OVEREXPRESSING THERAPEUTIC GROWTH FACTORS FOR THE TREATMENT OF EXPERIMENTAL RAT MYOCARDIAL INFARCTIONKonoplyannikov M, Haider K, Ashraf MWe tested the hypothesis that simultaneous transgenic overexpression of a select quartet of growth factors activates diverse signaling pathways for mobilization and participation of various stem/progenitor cells for cardiogenesis in the infarcted heart. IGF 1, VEGF, SDF 1α, and HGF plas mids were synthesized and transfected into rat skeletal myoblasts (SM). Overexpression of growth factors in transfected SM (TransSM) was confirmed by reverse transcription PCR, western blotting, and fluorescence immunostaining. The conditioned medium (CM) from TransSM was cytoprotective

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Stem cell factor induces HIF-1α at normoxia in hematopoietic cells

Cited by 67 publications

References 23 publications

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

The science behind the hypoxic niche of hematopoietic stem and progenitors

Transplantation of Genetic Modified Stem Cells Overexpressing Therapeutic Growth Factorsfor the Treatment of Experimental Rat Myocardial Infarction

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