Recruitment of Primitive Peripheral Blood Cells: Synergism of Interleukin 12 With Interleukin 6 and Stromal Cell-Derived Factor-1

Grafte-Faure, Stéphanie; Leveque, Catherine; Ketata, Elhem; Jean, P.; Vasse, Marc; Soria, Claudine; Vannier, Jean‐Pierre

doi:10.1006/cyto.1999.0520

Cited by 17 publications

(16 citation statements)

References 39 publications

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“…We found that 5-FU, like ionizing irradiation, induces the expression of SDF-1 by murine and human BM-derived osteoblasts and significantly increases homing and engraftment of SRC. It is suggested that increase in production of SDF-1 during alarm situations is part of host defense mechanism that counteracts the effects of DNA-damaging agents leading to cell death and anemia (17,18). The expression of SDF-1 demonstrated here, in conjunction with irradiation and chemotherapy treatment that are commonly used in clinical protocols, may also increase repopulation by malignant cells, since many cancer cells express CXCR4 and respond to stimulation with SDF-1.…”

Section: Discussionmentioning

confidence: 78%

“…These results demonstrate that long-term repopulation by pluripotent stem cells is impaired in CXCR4-null fetal liver cells, since these cells fail to durably proliferate and differentiate in the absence of CXCR4. In support of this notion, recent studies demonstrated that SDF-1 is a survival factor for both murine and human immature progenitor cells (17)(18)(19). Other studies indicate that SDF-1 is a pre-Bcell growth factor, that it is also involved in the development of megakaryocytes, that it is an inhibitor of myelopoiesis, and that it prevents primitive human cells from entering the cell cycle (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 85%

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Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function

Ponomaryov¹,

Peled²,

Petit³

et al. 2000

J. Clin. Invest.

542

486

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The chemokine stromal-derived factor-1 (SDF-1) controls many aspects of stem cell function. Details of its regulation and sites of production are currently unknown. We report that in the bone marrow, SDF-1 is produced mainly by immature osteoblasts and endothelial cells. Conditioning with DNAdamaging agents (ionizing irradiation, cyclophosphamide, and 5-fluorouracil) caused an increase in SDF-1 expression and in CXCR4-dependent homing and repopulation by human stem cells transplanted into NOD/SCID mice. Our findings suggest that immature osteoblasts and endothelial cells control stem cell homing, retention, and repopulation by secreting SDF-1, which also participates in host defense responses to DNA damage.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 85%

Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function

Ponomaryov¹,

Peled²,

Petit³

et al. 2000

J. Clin. Invest.

542

486

View full text Add to dashboard Cite

show abstract

“…This subsequently enhances their in vitro migration toward an SDF-1α gradient [27,29] and is also in agreement with our study. Low concentrations of SDF-1α together with other cytokines enhance the survival and proliferation of both human CD34 + cells and murine stem cells [30,31]. On the other hand the SDF-1α/CXCR4 interaction is also involved in the retention of stem and progenitor cells in the bone marrow [20,32,33].…”

Section: Discussionmentioning

confidence: 99%

Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium

Zhang

Fan

Zhou

et al. 2008

Journal of Molecular and Cellular Cardiology

257

218

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Bone marrow mesenchymal stem cells (MSCs) participate in myocardial repair following myocardial infarction. However, their in vivo reparative capability is limited due to lack of their survival in the infarcted myocardium. To overcome this limitation, we genetically engineered male rat MSCs overexpressing CXCR4 in order to maximize the effect of stromal cell-derived factor-1α (SDF-1α) for cell migration and regeneration. MSCs were isolated from adult male rats and cultured. Adenoviral transduction was carried out to over-express either CXCR4/green fluorescent protein (Ad-CXCR4/GFP) or Ad-null/GFP alone (control). Flow cytometry was used to identify and isolate GFP/CXCR4 over-expressing MSCs for transplantation. Female rats were assigned to one of four groups (n = 8 each) to receive GFP-transduced male MSCs (2 × 10 6 ) via tail vein injection 3 days after ligation of the left anterior descending (LAD) coronary artery: GFP-transduced MSCs (Ad-null/ GFP-MSCs, group 1) or MSCs over-expressing CXCR4/GFP (Ad-CXCR4/GFP-MSCs, group 2), or Ad-CXCR4/GFP-MSCs plus SDF-1α (50 ng/μl) (Ad-CXCR4/GFP-MSCs/SDF-1α, group 3), or Ad-miRNA targeting CXCR4 plus SDF-1α (Ad-miRNA/GFP-MSCs + SDF-1α treatment, group 4). Cardiodynamic data were obtained 4 weeks after induction of regional myocardial infarction (MI) using echocardiography after which hearts were harvested for immunohistochemical studies. The migration of GFP and Y-chromosome positive cells increased significantly in the peri-and infarct areas of groups 2 and 3 compared to control group (p<0.05), or miRNA-CXCR4 group (p<0.01). The number of CXCR4 positive cells in groups 2, 3 was intimately associated with angiogenesis and myogenesis. MSCs engraftment was blocked by pretreatment with miRNA (group 4). Cardiac function was significantly improved in rats receiving MSCs over-expressing CXCR4 alone or with SDF-1α. The up-regulation of matrix metalloproteinases (MMPs) by CXCR4 overexpressing MSCs perhaps facilitated their engraftment in the collagenous tissue of the infarcted area. CXCR4 overexpression led to enhance in vivo mobilization and engraftment of MSCs into ischemic area where these cells promoted neomyoangiogenesis and alleviated early signs of left ventricular remodeling.

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“…[24][25][26][27] We therefore monitored the effect of SDF-1 at low concentrations on proliferation of CXCR4-overexpressing cells. Transduced cells were incubated with SDF-1 (50 ng/mL) in combination with a cytokine cocktail (SCF, FLT-3L, and IL-6) known to support stem cells in vitro, and cell number was assessed at 24-hour intervals for 1 week.…”

Section: Cxcr4-transduced Cd34 ؉ Cells Are More Responsive To Low Sdfmentioning

confidence: 99%

“…Low concentrations of SDF-1 in synergy with other early acting cytokines enhance proliferation/survival of both human CD34 ϩ cells and murine stem cells. [24][25][26][27][28] High levels of SDF-1 induce quiescence of proliferating human LTCICs and primitive human fetal liver CD34 ϩ cells capable of serial repopulation of NOD/ SCID mice. 29,30 Of importance, SDF-1/CXCR4 interactions are also involved in retention of stem and progenitor cells in the BM.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation

Kahn

Byk

Jansson‐Sjöstrand

et al. 2004

Blood

212

158

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A major limitation to clinical stem cellmediated gene therapy protocols is the low levels of engraftment by transduced progenitors. We report that CXCR4 overexpression on human CD34 ؉ progenitors using a lentiviral gene transfer technique helped navigate these cells to the murine bone marrow and spleen in response to stromal-derived factor 1 (SDF-1) signaling. Cells overexpressing CXCR4 exhibited significant increases in SDF-1-mediated chemotaxis and actin polymerization compared with control cells. A major advantage of CXCR4 overexpression was demonstrated by the ability of transduced CD34 ؉ cells to respond to lower, physiologic levels of SDF-1 when compared to control cells, leading to improved SDF-1-induced migration and proliferation/survival, and finally resulting in significantly higher levels of in vivo repopulation of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice including primitive CD34 ؉ /CD38 ؊/low cells. Importantly, no cellular transformation was observed following transduction with the CXCR4 vector. Unexpectedly, we documented lack of receptor internalization in response to high levels of SDF-1, which can also contribute to increased migration and proliferation by the transduced CD34 ؉ cells. Our results suggest CXCR4 overexpression for improved definitive human stem cell motility, retention, and multilineage repopulation, which could be beneficial for in vivo navigation and expansion of hematopoietic progenitors. ( IntroductionGene transfer into human hematopoietic stem cells (HSCs) may be a promising tool in the correction of a wide variety of hematopoietic and genetic disorders. HSC transplantation can be used to durably deliver these genetically modified cells to the bone marrow (BM), which in turn will release mature cells with the corrected gene into the circulation throughout life. Clinical and experimental HSC transplantation procedures mimic the physiologic process of HSC migration from the circulation into the BM occurring during late embryonic development and steady-state hematopoiesis in adults throughout life. [1][2][3] One of the disadvantages of BM transplantation is the long-lasting reduced levels of immature progenitors, including long-term culture-initiating cells (LTCICs; 1 log reduction), in the BM of patients who have received transplants compared with healthy individuals. [4][5][6] Furthermore, emerging evidence exists for impaired homing 7 and low engraftment 8 of retrovirally transduced human CD34 ϩ cells. Enhanced efficacy of HSC engraftment could improve the outcome of clinical transplantations as well as gene therapy protocols and might be achieved by modulating the ability of stem cells to home to and repopulate the recipient BM.Interactions between the chemokine stromal-derived factor 1 (SDF-1), also referred to as CXCL12, and its receptor CXCR4 play an essential role in stem cell seeding of the BM during murine embryonic development. 9,10 Moreover, we have previously demonstrated in a functional preclinical model, using nonobese diabetic/ severe ...

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Recruitment of Primitive Peripheral Blood Cells: Synergism of Interleukin 12 With Interleukin 6 and Stromal Cell-Derived Factor-1

Cited by 17 publications

References 39 publications

Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function

Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function

Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium

Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation

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