Mobilization, endothelial differentiation and functional capacity of endothelial progenitor cells after ischemic stroke

Navarro-Sobrino, Míriam; Rosell, Anna; Hernández-Guillamón, Mar; Peñalba, Anna; Ribó, Marc; Álvarez-Sabín, José; Montaner, Joan

doi:10.1016/j.mvr.2010.05.008

Cited by 67 publications

(70 citation statements)

References 31 publications

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“…We did not observe a disease‐related increase in the number of BOEC colonies obtained, as was previously shown during active inflammation, tissue damage, and intense vascular remodeling (acute myocardial infarction,20 acute ischemic stroke,21, 22 rheumatoid arthritis,23 neovascular age‐related macular degeneration,24 or extensive burns25). In our patient population with stable ischemic heart failure, optimally treated according to current guidelines, a similar number of BOEC colonies were obtained in patients and healthy controls.…”

Section: Discussionsupporting

confidence: 85%

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Dauwe

Pelacho

Wibowo

et al. 2016

JAHA

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BackgroundBlood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in vitro and in vivo functionality of BOECs derived from ICMP with BOECs from age‐matched (ACON) and healthy young (CON) controls.Methods and ResultsWe isolated 3.6±0.6 BOEC colonies/100×106 mononuclear cells (MNCs) from 60‐mL blood samples of ICMP patients (n=45; age: 66±1 years; LVEF: 31±2%) versus 3.5±0.9 colonies/100×106 MNCs in ACON (n=32; age: 60±1 years) and 2.6±0.4 colonies/100×106 MNCs in CON (n=55; age: 34±1 years), P=0.29. Endothelial lineage (VEGFR2+/CD31+/CD146+) and progenitor (CD34+/CD133−) marker expression was comparable in ICMP and CON. Growth kinetics were similar between groups (P=0.38) and not affected by left ventricular systolic dysfunction, maladaptive remodeling, or presence of cardiovascular risk factors in ICMP patients. In vitro neovascularization potential, assessed by network remodeling on Matrigel and three‐dimensional spheroid sprouting, did not differ in ICMP from (A)CON. Secretome analysis showed a marked proangiogenic profile, with highest release of angiopoietin‐2 (1.4±0.3×105 pg/106 ICMP‐BOECs) and placental growth factor (5.8±1.5×103 pg/106 ICMP BOECs), independent of age or ischemic disease. Senescence‐associated β‐galactosidase staining showed comparable senescence in BOECs from ICMP (5.8±2.1%; n=17), ACON (3.9±1.1%; n=7), and CON (9.0±2.8%; n=13), P=0.19. High‐resolution microcomputed tomography analysis in the ischemic hindlimb of nude mice confirmed increased arteriogenesis in the thigh region after intramuscular injections of BOECs from ICMP (P=0.025; n=8) and CON (P=0.048; n=5) over vehicle control (n=8), both to a similar extent (P=0.831).Conclusions BOECs can be successfully culture‐expanded from patients with ICMP. In contrast to impaired functionality of ICMP‐derived bone marrow MNCs, BOECs retain a robust proangiogenic profile, both in vitro and in vivo, with therapeutic potential for targeting ischemic disease.

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Section: Discussionsupporting

confidence: 85%

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Dauwe

Pelacho

Wibowo

et al. 2016

JAHA

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“…In rat models of focal cerebral ischemia, administration of CD34 + EPCs improves functional outcomes (26,27). In humans, circulating levels of EPCs tend to track the temporal profile of recovery from 7 to 14 d after stroke onset (28,29). However, it remains unclear how EPCs are triggered for central neurovascular repair.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery

Hayakawa

Pham

Katušić

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

167

154

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Crosstalk between the brain and systemic responses in blood is increasingly suspected of playing critical roles in stroke. However, how this communication takes place remains to be fully understood. Here, we show that reactive astrocytes can release a damage-associated molecular-pattern molecule called high-mobilitygroup-box-1 (HMGB1) that promotes endothelial progenitor cell (EPC)-mediated neurovascular remodeling during stroke recovery. Conditioned media from reactive astrocytes increase EPC proliferation in vitro. siRNA suppression of HMGB1 in astrocytes or blockade of the HMGB1 receptor for advanced glycation endproducts in EPCs prevents this effect. In a mouse model of focal cerebral ischemia, reactive astrocytes in the peri-infarct cortex upregulate HMGB1 at 14 d poststroke, along with an accumulation of endogenous EPCs. In vivo siRNA suppression of HMGB1 blocks this EPC response, reduces peri-infact angiogenesis, and worsens neurological deficits. Taken together, these molecular and in vivo findings support a previously undescribed mechanism of crosstalk between reactive astrocytes and EPCs wherein HMGB1 promotes neurovascular remodeling and functional recovery after stroke and brain injury.reactive glia | vascular repair | brain remodeling

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“…They tended to be larger than functioning adenomas (25.2 ± 8.7 vs. 22.8 ± 8.4 mm, p = 0.16, Mann-Whitney U test), possibly because their growth was supported by neovascularization induced in the presence of relatively ischemic conditions. In fact, pituitary apoplexy triggered by ischemia was seen more often in patients with NFoma than the other pituitary adenoma subtypes [28,29] and endothelial progenitor cells including CD34/CD133/VEGFR2+ cells were generally mobilized into ischemic tissue from bone marrow [30]. Together, these observations suggest that CD133+ cells may represent an endothelial progenitor cell reserve that becomes activated under the ischemic conditions present in pituitary adenomas.…”

Section: Discussionmentioning

confidence: 99%

Identification of CD133+ Cells in Pituitary Adenomas

Yunoue¹,

Arita²,

Kawano³

et al. 2011

Neuroendocrinology

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Stem-like cells in tumors are capable of self-renewal and pluri-differentiation; they are thought to play important roles in tumor initiation and maintenance. Stem-like cells in malignant glioma express CD133. We examined samples from human pituitary adenoma, a generally benign neoplasm, for CD133 expression using routine immunohistochemical and biochemical methods. Our study of 70 pituitary adenomas (clinically nonfunctioning adenomas and growth hormone-, prolactin-, adrenocorticotropic hormone-, and thyroid-stimulating hormone-producing adenomas) showed that 18 (25.7%) expressed CD133. This rate was higher in clinically nonfunctioning (33.3%) than functioning adenomas (12.0%) (p = 0.085). Real-time PCR assay revealed the expression of CD133 mRNA in samples immunohistochemically positive for CD133. Neither the patient age and gender, nor the tumor size or postoperative recurrence rate correlated with CD133 positivity. CD133+ cells ubiquitously coexpressed CD34, nestin, and VEGFR2 (KDL1). S-100 and GFAP were not coexpressed with CD133. Chromogranin A, Pit-1, SF-1, and NeuroD1 were immune-negative, indicating that CD133+ cells did not have the potential to differentiate into functional endocrine cells. Our data suggest that the expression of CD133 in pituitary adenomas is related to immature endothelial progenitor cells that may play a role in the neovascularization of pituitary adenomas. Further studies are needed to elucidate the significance of CD133+ cells with respect to neovascularization and their sustainable growth in pituitary adenomas.

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Mobilization, endothelial differentiation and functional capacity of endothelial progenitor cells after ischemic stroke

Cited by 67 publications

References 31 publications

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery

Identification of CD133+ Cells in Pituitary Adenomas

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