Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury

Kähler, Christian M.; Wechselberger, Jutta; Hilbe, Wolfgang; Gschwendtner, Andreas; Colleselli, Daniela; Niederegger, Harald; Boneberg, Eva-Maria; Spizzo, Gilbert; Wendel, Albrecht; Gunsilius, Eberhard; Patsch, Josef R.; Hamacher, Jürg

doi:10.1186/1465-9921-8-50

Cited by 97 publications

(76 citation statements)

References 99 publications

(96 reference statements)

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“…VEGF induced CD31, VE-cadherin, TF, vWF, and SRF expression. D, cells (11th passage) were seeded on gelatin-coated plates and cocultured for one to three passages with 5 μg/mL AS or AS-Tspan8 exosomes or VEGF: morphology (scale bar: 100 μm) and gene expression (RT-PCR) after one and three passages in comparison with RAEC, BMC, and BMC-derived ECP (31). In cocultures with 5 μg/mL AS-Tspan8 exosomes, ECPs start to form cable-like structures, lose CD133 and VEGFR2, but gain CD31 and VEGFR1 expression, resembling mature ECs.…”

Section: and Cd11bmentioning

confidence: 99%

Cell Surface Tetraspanin Tspan8 Contributes to Molecular Pathways of Exosome-Induced Endothelial Cell Activation

et al. 2010

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Tumor-derived exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into exosomes, including CD106 and CD49d, which were implicated in exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis.

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Section: and Cd11bmentioning

confidence: 99%

Cell Surface Tetraspanin Tspan8 Contributes to Molecular Pathways of Exosome-Induced Endothelial Cell Activation

et al. 2010

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“…In addition to the securely established effects on cancer and immunodeficiency engraftment of bone-marrow-derived cells (BMDC) into lung tissue and cerebellum has been proposed. 7 At the face of Purkinje cell loss and progressive lung destruction several studies have shown that BMDC are able to contribute to neogenesis of cerebellar Purkinje neurons or lung tissue regeneration and protection which is of special interest for a therapeutic approach for A-T. 8,9 In Atm-deficient mice, BMT significantly inhibited tumorigenesis and improved the immunity, weight gain and fitness. 10,11 Our results further showed the migration of CD31 +CD45-endothelial cells and EpCAM+ epithelial cells into the lung tissue of transplanted Atm-deficient mice.…”

Section: Introductionmentioning

confidence: 99%

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice

Pietzner¹,

Merscher²,

Baer³

et al. 2016

Bone Marrow Transplant

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Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a coconditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atmdeficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model.

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“…1A). 12 The phenotypes of cultured cells were further characterized according to their ability for uptake of Dil-labeled acetylated-LDL to confirm their endothelial lineage. We incubated the adherent cells with 10 mg/mL Dil-Ac-LDL (Biomedical Technologies, Stoughton, MA) at 378C for 4 h. After the incubation, cells were fixed with 3% formaldehyde for 20 min and viewed under a fluorescent microscope.…”

mentioning

confidence: 99%

Endothelial progenitor cells promote fracture healing in a segmental bone defect model

Ateşok

Stewart

et al. 2010

Journal Orthopaedic Research

103

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The objective of this study was to evaluate the effects of local endothelial progenitor cell (EPC) therapy on bone regeneration in a rat model. A segmental bone defect (5 mm) was created in the femur and fixed with a mini-plate. There were two groups: EPC-treated (N ¼ 28) and control (N ¼ 28). Seven animals were sacrificed from each group at 1, 2, 3, and 10 weeks postoperatively. Healing of the defect was evaluated with radiographic, histological, and quantitative micro-computed tomography (micro-CT) scans. Radiographically, mean scores of the EPC and control groups were, respectively, 1.16-0.61 (p < 0.05) at 1 week, 2.53-1.54 (p < 0.05) at 2 weeks, and 4.58-2.35 at 3 weeks (p < 0.05). At 10 weeks, all the animals in the EPC-treated group had complete union (7/7), but in the control group none achieved union (0/7). Histological evaluation revealed that specimens from EPC-treated animals had abundant new bone and vessel formation compared to that in controls. Micro-CT assessment of the samples from the animals sacrificed at 10 weeks (N ¼ 14) showed significantly improved parameters of bone volume (36.58-10.57, p ¼ 0.000), bone volume density (0.26-0.17, p ¼ 0.000), model index À2.22-2.79, p ¼ 0.000), trabecular number (1.28-0.91, p ¼ 0.063), trabecular thickness (0.21-0.15, p ¼ 0.001), trabecular spacing (0.63-1.07, p ¼ 0.022), bone surface (353.75-152.08, p ¼ 0.000), and bone surface to bone volume ratio (9.54-14.24, p ¼ 0.004) for the EPC group compared to control, respectively. In conclusion, local EPC therapy significantly enhanced bone regeneration in a segmental defect model in rat femur diaphysis. ß

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Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury

Cited by 97 publications

References 99 publications

Cell Surface Tetraspanin Tspan8 Contributes to Molecular Pathways of Exosome-Induced Endothelial Cell Activation

Cell Surface Tetraspanin Tspan8 Contributes to Molecular Pathways of Exosome-Induced Endothelial Cell Activation

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice

Endothelial progenitor cells promote fracture healing in a segmental bone defect model

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