Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients

Kukumberg, Marek; Zaw, Aung Moe; Wong, Daniel Hc; Toh, Chin Min; Chan, Bernard P.L.; Seet, Raymond C.S.; Wong, Peiyan; Yim, Evelyn K.F.

doi:10.1007/s12015-020-10064-z

Cited by 24 publications

(27 citation statements)

References 66 publications

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“…Although accumulating evidence has suggested that cardiovascular risk factors are associated with dysfunction and a reduced number of EPCs [ 34 – 37 ], the influence of cerebrovascular diseases on circulating EPCs is still debated. For instance, studies have shown that stroke was associated with a reduced number of circulating EPCs [ 38 ] and impairment of EPC function [ 39 , 40 ]. On the other hand, some studies have also reported an increase in the number of circulating EPCs in stroke patients [ 16 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage

et al. 2021

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Background Cell-based therapeutic strategies have been proposed as an alternative for brain repair after stroke, but their clinical application has been hampered by potential adverse effects in the long term. The present study was designed to test the effect of the secretome of endothelial progenitor cells (EPCs) from stroke patients (scCM) on in vitro human models of angiogenesis and vascular barrier. Methods Two different scCM batches were analysed by mass spectrometry and a proteome profiler. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used for designing angiogenesis studies (proliferation, migration, and tubulogenesis) or in vitro models of EC monolayer (confluent monolayer ECs—CMECs) and blood–brain barrier (BBB; brain-like ECs—BLECs). Cells were treated with scCM (5 μg/mL) or protein-free endothelial basal medium (scEBM—control). CMECs or BLECs were exposed (6 h) to oxygen–glucose deprivation (OGD) conditions (1% oxygen and glucose-free medium) or normoxia (control—5% oxygen, 1 g/L of glucose) and treated with scCM or scEBM during reoxygenation (24 h). Results The analysis of different scCM batches showed a good reproducibility in terms of protein yield and composition. scCM increased CD34+-EC proliferation, tubulogenesis, and migration compared to the control (scEBM). The proteomic analysis of scCM revealed the presence of growth factors and molecules modulating cell metabolism and inflammatory pathways. Further, scCM decreased the permeability of CMECs and upregulated the expression of the junctional proteins such as occludin, VE-cadherin, and ZO-1. Such effects were possibly mediated through the activation of the interferon pathway and a moderate downregulation of Wnt signalling. Furthermore, OGD increased the permeability of both CMECs and BLECs, while scCM prevented the OGD-induced vascular leakage in both models. These effects were possibly mediated through the upregulation of junctional proteins and the regulation of MAPK/VEGFR2 activity. Conclusion Our results suggest that scCM promotes angiogenesis and the maturation of newly formed vessels while restoring the BBB function in ischemic conditions. In conclusion, our results highlight the possibility of using EPC-secretome as a therapeutic alternative to promote brain angiogenesis and protect from ischemia-induced vascular leakage.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage

et al. 2021

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“…Several studies shown that the accumulation of risk factors and the presence of coronary, cerebral, or peripheral atherosclerosis are associated with dysfunction and reduced numbers of EPCs [ 14 , 17 , 24 , 27 – 29 ]. EPCs are a promising therapeutic target for IS [ 30 , 31 ] although the limited availability in blood of LOECs and the limited availability and early senescence of isolated CACs in culture conditions adversely affect its application as effective therapy [ 31 – 33 ]. Moreover, vascular injury or disease may be associated with activation of osteogenic genes by EPCs which could promote vascular calcification rather than normal repair processes.…”

Section: Discussionmentioning

confidence: 99%

“…Second, CFU-ECs comprise a heterogeneous population of monocytes and T cells with distinct physiological properties [ 51 ]. Third, we did not evaluated the vasculogenic function [ 31 ] and the EPC secretome [ 52 ], and these determinants should be considered prior to evaluating the therapeutic role of EPCs in patients with IS patients. Fourth, patients who received thrombolytic treatment had more severe symptoms and large size of ischemic stroke than those who did not receive thrombolysis treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of circulating angiogenic cells in patients with ischemic stroke

Rodrı́guez-Esparragón

Torres-Mata

López-Fernández

et al. 2022

BMC Cardiovasc Disord

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Background Endothelial progenitor cells (EPCs) are circulating angiogenic cells with endothelial features associated with risk for stroke. We aimed to delve into their functional characteristics. EPCs were isolated and cultured from Ischemic Stroke (IS) patients and predictors of their variance evaluated. Methods This is a single-center observational study evaluating 187 consecutively hospitalized patients with IS. EPCs were isolated from blood samples. The number of circulating angiogenic cells (CACs), colony-forming units (CFU-ECs) and the emergence of late outgrowths endothelial cells (LOECs) were counted. We collected clinical variables and measured the stromal cell-derived factor 1 alpha (SDF1α) serum levels. We also examined the relative telomere length and the expression of osteogenic gene markers in CACs. Results CACs counts and CFU-ECs colony numbers were positively correlated (rho = 0.41, p < 0.001, n = 187). We found significant differences according to whether thrombolytic treatment was performed in the distribution of CFU-ECs (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.01–6.35; p = 0.042) and CACs (OR = 4.45; 95% IC 1.2–15.5; p = 0.012). The main determinants of CACs variation were the number of risks factors, thrombolysis treatment, arterial hypertension, LOECs occurrence, and the vascular endothelial growth factor expression, whereas CFU-ECs variations depended on hemoglobin content and the relative reduction in the National Institutes of Health Stroke Scale (NIHSS) criteria. The main predictors of LOECs appearance were thrombolysis and length of hospital stay. Conclusions Our study supports the relevance of patient risk factors and treatments in the analysis of the functional properties of EPCs.

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“…EPCs are the key cell types involved in angiogenesis; they migrate to injury/ischemia sites and promote angiogenesis at the wound surface [ 44 ]. Although the vast majority of studies on EPCs have focused on the treatment of stroke [ 45 ] and other vascular diseases [ 46 , 47 ], recent studies have suggested that EPCs may be used for skin wound healing.…”

Section: Discussionmentioning

confidence: 99%

Experimental Study on the Effect of Allogeneic Endothelial Progenitor Cells on Wound Healing in Diabetic Mice

Leng

Peng

Pan

et al. 2021

Journal of Diabetes Research

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Endothelial progenitor cells (EPCs) are involved in the neovascularization in traumatic and ischemic sites, but EPCs are “detained” in bone marrow under diabetic conditions, which results in reduction of the number of EPCs and their biological activity in peripheral blood. Based on our previous study to mobilize autologous bone marrow EPCs by administering AMD3100+G-CSF to realize the optimal effect, our present study is aimed at exploring the effects of transplanting EPCs locally in a wound model of diabetic mice. First, we prepared and identified EPCs, and the biological functions and molecular characteristics were compared between EPCs from DB/+ and DB/DB mice. Then, we performed full-thickness skin resection in DB/DB mice and tested the effect of local transplantation of EPCs on skin wound healing. The wound healing process was recorded using digital photographs. The animals were sacrificed on postoperative days 7, 14, and 17 for histological and molecular analysis. Our results showed that DB/+ EPCs were biologically more active than those of DB/DB EPCs. When compared with the control group, local transplantation of EPCs accelerated wound healing in DB/DB mice by promoting wound granulation tissue formation, angiogenesis, and collagen fiber deposition, but there was no significant difference in wound healing between DB/+ EPCs and DB/DB EPCs transplanted into the wound. Furthermore, local transplantation of EPCs promoted the expression of SDF-1, CXCR4, and VEGF. We speculated that EPC transplantation may promote wound healing through the SDF-1/CXCR4 axis. This point is worth exploring further. Present data are of considerable significance because they raise the possibility of promoting wound healing by isolating autologous EPCs from the patient, which provides a new approach for the clinical treatment of diabetic wounds in the future.

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Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients

Cited by 24 publications

References 66 publications

RETRACTED ARTICLE: Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage

RETRACTED ARTICLE: Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage

Clinical relevance of circulating angiogenic cells in patients with ischemic stroke

Experimental Study on the Effect of Allogeneic Endothelial Progenitor Cells on Wound Healing in Diabetic Mice

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