Mobilization of endothelial progenitor cells into the circulation in burned patients

Fox, Andreas; Smythe, Jon; Fisher, Nita; Tyler, Michael; McGrouther, Duncan Angus; Watt, Suzanne M.; Harris, Adrian L.

doi:10.1002/bjs.5913

Cited by 80 publications

(62 citation statements)

References 30 publications

(38 reference statements)

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“…Both VEGF and G-CSF are cytokines implicated in the acute mobilization of endothelial progenitor cells by VDAs (13). In our study, CEC and CEPC numbers were so low (on average less than 50 cells/mL) that these cell populations were not quantifiable with confidence, although the same standardized method detected changes in burns patients (34,35), patients in a phase I trial of antiangiogenic therapy (36) and patients on OXi4503, another VDA (13,35). However, the numbers of the overall bone marrow progenitor population CD45 À /dim CD34 þ or CD133 þ cell populations did increase significantly following treatment and the CEC or CEPC populations form a small part of these larger cell populations.…”

Section: Discussionmentioning

confidence: 57%

Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer

Nathan

Zweifel

Padhani

et al. 2012

Clinical Cancer Research

156

119

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Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m 2 on day 1, day 8, and then every 14 days. Bevacizumab 10 mg/kg was given on day 8 and at subsequent cycles four hours after CA4P. Functional imaging with dynamic contrast enhanced-MRI (DCE-MRI) was conducted at baseline, after CA4P alone, and after cycle 1 CA4P þ bevacizumab.Results: A total of 63 mg/m 2 CA4P þ 10 mg/kg bevacizumab q14 is the recommended phase II dose. A total of 15 patients were enrolled. Dose-limiting toxicities were grade III asymptomatic atrial fibrillation and grade IV liver hemorrhage in a patient with a history of hemorrhage. Most common toxicities were hypertension, headache, lymphopenia, pruritus, and pyrexia. Asymptomatic electrocardiographic changes were seen in five patients. Nine of 14 patients experienced disease stabilization. A patient with ovarian cancer had a CA125 response lasting for more than a year. DCE-MRI showed statistically significant reductions in tumor perfusion/vascular permeability, which reversed after CA4P alone but which were sustained following bevacizumab. Circulating CD34 þ and CD133 þ bone marrow progenitors increased following CA4P as did VEGF and granulocyte colony-stimulating factor levels. Conclusions: CA4P in combination with bevacizumab appears safe and well tolerated in this dosing schedule. CA4P induced profound vascular changes, which were maintained by the presence of bevacizumab.

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Section: Discussionmentioning

confidence: 57%

Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer

Nathan

Zweifel

Padhani

et al. 2012

Clinical Cancer Research

156

119

View full text Add to dashboard Cite

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“…Our approach to examining the effects of AMD3100 in a complex in vitro microenvironmental model of neovascularization may prove significant for understanding the mechanisms of action of this and other drugs and associated molecules in promoting or inhibiting revascularization and for more clearly defining the experimental approach to testing or assessing the effects of such drugs in vitro and subsequently in vivo. Understanding such mechanisms as those exemplified here with CXCL12 in new blood vessel formation has translational implications that include inhibition of tumor progression and promotion of tissue repair and regeneration as diverse as peripheral arterial disease and ischemic injury, burn injury, neurodegenerative disease, and hematological regeneration [5][6][7]11,18,22,[56][57][58][59][60].…”

Section: Fig 6 Cd31 Blocks Integration Of Exogenous Huvecs Into Immmentioning

confidence: 99%

“…These include hematopoietic stem/ progenitor cell (HSC/HPC) trafficking, immune surveillance, blood vessel, cardiac and central nervous system formation during development, revascularization at sites of tissue injury, and the initiation and metastatic spread of tumors [1][2][3][4][5][6][7][8][9]. CXCL12 plasma levels are rapidly elevated in response to tissue damage, with increased CXCL12 concentrations correlating with the severity of injury, increased vascular endothelial growth factor (VEGF) plasma levels, and the associated rapid mobilization of proangiogenic cells into the circulation [10,11].…”

Section: Introductionmentioning

confidence: 99%

The Hematopoietic Chemokine CXCL12 Promotes Integration of Human Endothelial Colony Forming Cell–Derived Cells into Immature Vessel Networks

Newey

Tsaknakis

Khoo

et al. 2014

Stem Cells and Development

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“…Previous results have indicated that mesenchymal stem cell-associated CD34 -/VE-cadherin -/AC133 + /Flk-1 + multipotent adult progenitor cells (MAPCs) may be converted to CD34 + /VE-cadherin -/AC133 -/Flk + angioblasts by the action of VEGF and that these cells may be further differentiated into mature endothelial cells (23,29,30) and become involved in tumor angiogenesis and wound healing. The cell surface markers of EPCs have not been fully elucidated and there continues to be large variances in the reported quantities of EPCs present in the circulation and uncertainty regarding the best enrichment and isolation methods (31,32). Thus, the specific phenotype that may distinguish EPCs from hematopoietic cells or mature endothelial cells still requires further exploration, which provides the motivation for continued progression in the method described in the present study.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester-labeled microspheres for detecting endothelial progenitor cells in human peripheral blood

Qiu

Zhang

Chi

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aims of the present study were to establish a single-platform f low cytometry method using 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled microspheres as the reference for determining endothelial progenitor cell (EPC) number and to evaluate the efficacy of this detection method. Single-platform flow cytometry was used to count cell numbers using CFSE-stained fluorescent microspheres as the internal reference and the EPC numbers in specimens using this novel method were compared with an in vitro clonogenic counting assay. The results of the two counting methods were consistent and compared with the in vitro clonogenic counting assay, the time and cost of the novel method was markedly reduced, as were the corresponding technical requirements. The present findings indicated that single-platform flow cytometry, with CFSE-labeled microspheres as the reference, provides faster and improved detection of EPCs in human peripheral blood specimens, with reduced time and cost, making it more suitable for routine clinical application. IntroductionThe occurrence, development and metastasis of tumors are closely related to angiogenesis due to the fact that blood vessels provide the necessary oxygen supply, nutrition, metabolite and avenue for metastasis to maintain the rapid growth of tumors (1-3). Angiogenesis, which is the generation of novel blood vessels, occurs by two completely different processes (4-6). In the first, the required vascular endothelial cells arise from the sprouting of existing blood vessels. In the second, they are derived from recruited endothelial precursor cells, which are a type of blast cell with the potential to differentiate into clonal endothelial cells in vitro as well as participate in cardiovascular generation in vivo (7). On their surface, they characteristically express cluster of differentiation (CD)34, vascular endothelial growth factor receptor 2 (VEGFR2) or kinase domain receptor (8,9).A large number of basic and clinical studies have indicated that the number of endothelial progenitor cells (EPCs) is closely related to tumor size, prognosis and therapy response (10-13). Evidence from animal models suggests that the EPC level in the peripheral circulation has some relevance to tumor volume (13). The number of EPCs in circulation has been identified to alter with anti-tumor and anti-angiogenesis therapies. Igreja et al (14) suggested that the EPC level in the peripheral blood of patients with lymphoma was related to the efficacy of the therapy. This hypothesis was supported by the fact that the EPC level in patients with complete remission decreased, while EPC levels continued to rise or did not change in those with partial remission or no response to therapy. In addition, it was revealed that tumor size and angiogenesis were associated with the number of EPCs in lymph nodes. Ho et al (15) indicated that, in patients with advanced non-surgically treated hepatocellular carcinoma (HCC), the EPC level in circulation was significantly higher compared w...

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Mobilization of endothelial progenitor cells into the circulation in burned patients

Abstract: Thermal injury induced a rapid rise in EPCs that was proportional to the extent of the burn and significantly correlated with levels of angiogenic cytokines. Such cytokines may be used to stimulate EPCs as a future therapeutic target in burned patients.

Cited by 80 publications

References 30 publications

Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer

Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer

The Hematopoietic Chemokine CXCL12 Promotes Integration of Human Endothelial Colony Forming Cell–Derived Cells into Immature Vessel Networks

Clinical significance of 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester-labeled microspheres for detecting endothelial progenitor cells in human peripheral blood

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