ijms-logo

Journal Browser

Journal Browser

Special Issue "Endothelial Progenitor Cells in Health and Disease"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 December 2020).

Special Issue Editors

Dr. Jolanta Weaver
E-Mail Website
Guest Editor
Institute of Cellular Medicine, Newcastle University, Newcastle, UK
Interests: cardiovascular disease; diabetes mellitus; vascular stem cells; endothelial progenitor cells; repurposing Metformin for CVD; risk factors for CVD; in-vitro models of CVD
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Germano Guerra
E-Mail Website
Guest Editor
Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy
Interests: endothelial progenitor cells; endothelial colony forming cells; myeloid angiogenic cells; regenerative medicine; antiangiogenic treatments; angiogenesis; vasculogenesis
Dr. Francesco Moccia
E-Mail Website
Guest Editor
Laboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Interests: Ca2+ signaling; angiogenesis; endothelial cells; endothelial progenitor cells; neurovascular coupling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endothelial progenitor cells (EPCs) represent a subpopulation of mononuclear cells (MNCs) that are recruited to replace senescent/injured vascular endothelial cells and to reconstruct injured vessels and restore local blood flow upon an ischemic insult. Furthermore, EPCs play a crucial role during the angiogenic switch that supports vascularization, growth, and metastasis in solid tumors. As proposed in a recent consensus statement, two distinct and well-defined EPC subtypes may emerge from cultured mononuclear cells, which differ in their ontology and reparative mechanisms. These EPC subtypes include: myeloid angiogenic cells (MACs), also termed circulating angiogenic cells (CACs), pro-angiogenic hematopoietic cells (PAC), pro-angiogenic circulating hematopoietic stem/progenitor cells (pro-CHSPCs or pro-CPCs), or “early” EPCs; and endothelial colony-forming cells (ECFCs), also known as outgrowth endothelial cells (OECs) or “late” EPCs. EPCs may support neovascularization of ischemic tissues through the paracrine release of growth factors and cytokines, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1a (SDF-1a), or by physically incorporating within nascent neovessels. Autologous MACs were probed in no less than 150 registered interventional clinical trials to induce therapeutic angiogenesis in multiple cardiovascular disorders, including myocardial infarction, critical limb ischemia, leg ulcer/gangrene, peripheral artery disease, hypertension, diabetic microvasculopathy, and stroke. Moreover, interfering with EPC recruitment to tumor sites is regarded as an alternative strategy to interfere with tumor growth and metastasis in cancer patients. We are witnessing a fascinating period of ground-breaking discoveries in the field, which encompass a vibrant discussion on the real meaning of the term EPC and the evaluation of multiple approaches to improve their efficiency for regenerative purposes.  

We are, therefore, pleased to invite all of you to participate to this Special Issue “Endothelial Progenitor Cells in Health and Diseases” by presenting your most recent research or ideas about the definition, identity, pathophysiology, and therapeutic application of EPCs. Experimental papers, up-to-date review articles, and commentaries are all welcome.

Dr. Francesco Moccia
Dr. Germano Guerra
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • endothelial progenitor cells
  • endothelial colony-forming cells
  • myeloid angiogenic cells
  • regenerative medicine
  • antiangiogenic treatments
  • angiogenesis
  • vasculogenesis

Related Special Issue

Published Papers (8 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction
Int. J. Mol. Sci. 2021, 22(18), 10159; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810159 - 21 Sep 2021
Viewed by 454
Abstract
Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and [...] Read more.
Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Figure 1

Article
Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells
Int. J. Mol. Sci. 2021, 22(18), 9696; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189696 - 08 Sep 2021
Viewed by 456
Abstract
Immunosuppressants are a mandatory therapy for transplant patients to avoid rejection of the transplanted organ by the immune system. However, there are several known side effects, including alterations of the vasculature, which involve a higher occurrence of cardiovascular events. While the effects of [...] Read more.
Immunosuppressants are a mandatory therapy for transplant patients to avoid rejection of the transplanted organ by the immune system. However, there are several known side effects, including alterations of the vasculature, which involve a higher occurrence of cardiovascular events. While the effects of the commonly applied immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (Tac) on mature endothelial cells have been addressed in several studies, we focused our research on the unexplored effects of CsA and Tac on endothelial colony-forming cells (ECFCs), a subgroup of endothelial progenitor cells, which play an important role in vascular repair and angiogenesis. We hypothesized that CsA and Tac induce functional defects and activate an inflammatory cascade via NF-κB signaling in ECFCs. ECFCs were incubated with different doses (0.01 µM–10 µM) of CsA or Tac. ECFC function was determined using in vitro models. The expression of inflammatory cytokines and adhesion molecules was explored by quantitative real-time PCR and flow cytometry. NF-κB subunit modification was assessed by immunoblot and immunofluorescence. CsA and Tac significantly impaired ECFC function, including proliferation, migration, and tube formation. TNF-α, IL-6, VCAM, and ICAM mRNA expression, as well as PECAM and VCAM surface expression, were enhanced. Furthermore, CsA and Tac led to NF-κB p65 subunit phosphorylation and nuclear translocation. Pharmacological inhibition of NF-κB by parthenolide diminished CsA- and Tac-mediated proinflammatory effects. The data of functional impairment and activation of inflammatory signals provide new insight into mechanisms associated with CsA and Tac and cardiovascular risk in transplant patients. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Graphical abstract

Article
Circulating Endothelial Progenitor Cells Are Preserved in Female Mice Exposed to Ambient Fine Particulate Matter Independent of Estrogen
Int. J. Mol. Sci. 2021, 22(13), 7200; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137200 - 04 Jul 2021
Viewed by 694
Abstract
Males have a higher risk for cardiovascular diseases (CVDs) than females. Ambient fine particulate matter (PM) exposure increases CVD risk with increased reactive oxygen species (ROS) production and oxidative stress. Endothelial progenitor cells (EPCs) are important to vascular structure and function and can [...] Read more.
Males have a higher risk for cardiovascular diseases (CVDs) than females. Ambient fine particulate matter (PM) exposure increases CVD risk with increased reactive oxygen species (ROS) production and oxidative stress. Endothelial progenitor cells (EPCs) are important to vascular structure and function and can contribute to the development of CVDs. The aims of the present study were to determine if sex differences exist in the effect of PM exposure on circulating EPCs in mice and, if so, whether oxidative stress plays a role. Male and female C57BL/6 mice (8–10 weeks old) were exposed to PM or a vehicle control for six weeks. ELISA analysis showed that PM exposure substantially increased the serum levels of IL-6 and IL-1β in both males and females, but the concentrations were significantly higher in males. PM exposure only increased the serum levels of TNF-α in males. Flow cytometry analysis demonstrated that ROS production was significantly increased by PM treatment in males but not in females. Similarly, the level of circulating EPCs (CD34+/CD133+ and Sca-1+/Flk-1+) was significantly decreased by PM treatment in males but not in females. Antioxidants N-acetylcysteine (NAC) effectively prevented PM exposure-induced ROS and inflammatory cytokine production and restored circulating EPC levels in male mice. In sharp contrast, circulating EPC levels remained unchanged in female mice with PM exposure, an effect that was not altered by ovariectomy. In conclusion, PM exposure selectively decreased the circulating EPC population in male mice via increased oxidative stress without a significant impact on circulating EPCs in females independent of estrogen. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Figure 1

Article
MicroRNA Profiles of Maternal and Neonatal Endothelial Progenitor Cells in Preeclampsia
Int. J. Mol. Sci. 2021, 22(10), 5320; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105320 - 18 May 2021
Viewed by 754
Abstract
Preeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children’s health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, [...] Read more.
Preeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children’s health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, although causative factors for the latter have remained elusive. MicroRNA (miRNA) modifications are a potential mechanism through which exposure to an altered environment translates into the development of chronic disease. In this study, we examined whether development of preeclampsia corresponds to alterations of miRNAs in maternal- and cord-blood-derived EPC. To test this end, we analyzed maternal and neonatal miRNAs via RNA sequencing from endothelial cells of preeclamptic and healthy controls in different cell culture passages. We were able to demonstrate differentially represented miRNAs in all groups. Hsa-miR-1270 showed significantly different levels in cord blood EPC from preeclampsia versus control and was negatively correlated with mRNA levels of its predicted targets ANGPTL7 and TFRC. Transfection with an hsa-miR-1270 inhibitor decreased the tube formation capacity and chemotactic motility but did not change proliferation in vitro. Target predictions and gene set enrichment analyses identified alternative splicing as a significantly enriched pathway for hsa-miR-1270. The top miRNAs in three other groups were predicted to target transcriptional and developmental pathways. Here, we showed for the first time significantly different levels of miRNAs and differently represented mRNA levels of predicted target genes in EPC derived from preeclampsia. Understanding the effects of preeclampsia on the epigenetic mechanisms of EPC will be crucial and may provide initial insights for further evaluation of the benefits of therapies targeting this cell population. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Figure 1

Article
A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial–Mesenchymal Transition
Int. J. Mol. Sci. 2021, 22(10), 5210; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105210 - 14 May 2021
Cited by 1 | Viewed by 522
Abstract
Therapeutic elevation of high-density lipoprotein (HDL) is thought to minimize atherogenesis in subjects with dyslipidemia. However, this is not the case in clinical practice. The function of HDL is not determined by its concentration in the plasma but by its specific structural components. [...] Read more.
Therapeutic elevation of high-density lipoprotein (HDL) is thought to minimize atherogenesis in subjects with dyslipidemia. However, this is not the case in clinical practice. The function of HDL is not determined by its concentration in the plasma but by its specific structural components. We previously identified an index for the prediction of HDL functionality, relative HDL (rHDL) index, and preliminarily explored that dysfunctional HDL (rHDL index value > 2) failed to rescue the damage to endothelial progenitor cells (EPCs). To confirm the effectiveness of the rHDL index for predicting HDL functions, here we evaluated the effects of HDL from patients with different rHDL index values on the endothelial–mesenchymal transition (EndoMT) of EPCs. We also analyzed the lipid species in HDL with different rHDL index values and investigated the structural differences that affect HDL functions. The results indicate that HDL from healthy adults and subjects with an rHDL index value < 2 protected transforming growth factor (TGF)-β1-stimulated EndoMT by modulating Smad2/3 and Snail activation. HDL from subjects with an rHDL index value > 2 failed to restore the functionality of TGF-β1-treated EPCs. Lipidomic analysis demonstrated that HDL with different rHDL index values may differ in the composition of triglycerides, phosphatidylcholine, and phosphatidylinositol. In conclusion, we confirmed the applicability of the rHDL index value to predict HDL function and found structural differences that may affect the function of HDL, which warrants further in-depth studies. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Figure 1

Article
PDLCs and EPCs Co-Cultured on Ta Discs: A Golden Fleece for “Compromised” Osseointegration
Int. J. Mol. Sci. 2021, 22(9), 4486; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094486 - 26 Apr 2021
Viewed by 532
Abstract
Material research in tissue engineering forms a vital link between basic cell research and animal research. Periodontal ligament cells (PDLCs, P) from the tooth have an osteogenic effect, whereas endothelial progenitor cells (EPCs, E) assist in neovascularization. In the present study, the interaction [...] Read more.
Material research in tissue engineering forms a vital link between basic cell research and animal research. Periodontal ligament cells (PDLCs, P) from the tooth have an osteogenic effect, whereas endothelial progenitor cells (EPCs, E) assist in neovascularization. In the present study, the interaction of PDLCs and EPCs with Tantalum (Ta, I) discs, either alone (IP or IE group) or in 1:1 (IPE) ratio was explored. Additionally, surface analysis of Ta discs with respect to different types and cycles of sterilization and disinfection procedures was evaluated. It was observed that Ta discs could be used for a maximum of three times, after which the changes in properties of Ta discs were detrimental to cell growth, irrespective of the type of the protocol. Cell-Disc’s analysis revealed that cell proliferation in the IE group at day 6 and day 10 was significantly higher (p < 0.05) than other groups. A cell viability assay revealed increased live cells in the IPE group than in the IP or IE group. Similarly, adhesion and penetration of cells in the IPE group were not only higher, but also had an increased thickness of cellular extensions. RT-PCR analysis revealed that on day 8, both osteogenic (ALP, RUNX-2, and BSP) and angiogenic genes (VEGFR-2, CD31) increased significantly in the IPE group as compared to the IP or IE groups (p < 0.05). In conclusion, Ta discs promoted cellular proliferation and increased osteogenic and angiogenic activity by augmenting RUNX-2 and VEGFR-2 activity. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Graphical abstract

Article
Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3+/Pod+/CD11b+ Cells) in Patient with Preeclampsia
Int. J. Mol. Sci. 2021, 22(8), 4237; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084237 - 19 Apr 2021
Cited by 1 | Viewed by 537
Abstract
The abnormal development or disruption of the lymphatic vasculature has been implicated in metabolic and hypertensive diseases. Recent evidence suggests that the offspring exposed to preeclampsia (PE) in utero are at higher risk of long-term health problems, such as cardiovascular and metabolic diseases [...] Read more.
The abnormal development or disruption of the lymphatic vasculature has been implicated in metabolic and hypertensive diseases. Recent evidence suggests that the offspring exposed to preeclampsia (PE) in utero are at higher risk of long-term health problems, such as cardiovascular and metabolic diseases in adulthood, owing to in utero fetal programming. We aimed to investigate lymphangiogenic activities in the lymphatic endothelial progenitor cells (LEPCs) of the offspring of PE. Human umbilical cord blood LEPCs from pregnant women with severe PE (n = 10) and gestationally matched normal pregnancies (n = 10) were purified with anti-vascular endothelial growth factor receptor 3 (VEGFR3)/podoplanin/CD11b microbeads using a magnetic cell sorter device. LEPCs from PE displayed significantly delayed differentiation and reduced formation of lymphatic endothelial cell (LEC) colonies compared with the LEPCs from normal pregnancies. LECs differentiated from PE-derived LEPCs exhibited decreased tube formation, migration, proliferation, adhesion, wound healing, and 3D-sprouting activities as well as increased lymphatic permeability through the disorganization of VE-cadherin junctions, compared with the normal pregnancy-derived LECs. In vivo, LEPCs from PE showed significantly reduced lymphatic vessel formation compared to the LEPCs of the normal pregnancy. Gene expression analysis revealed that compared to the normal pregnancy-derived LECs, the PE-derived LECs showed a significant decrease in the expression of pro-lymphangiogenic genes (GREM1, EPHB3, VEGFA, AMOT, THSD7A, ANGPTL4, SEMA5A, FGF2, and GBX2). Collectively, our findings demonstrate, for the first time, that LEPCs from PE have reduced lymphangiogenic activities in vitro and in vivo and show the decreased expression of pro-lymphangiogenic genes. This study opens a new avenue for investigation of the molecular mechanism of LEPC differentiation and lymphangiogenesis in the offspring of PE and subsequently may impact the treatment of long-term health problems such as cardiovascular and metabolic disorders of offspring with abnormal development of lymphatic vasculature. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Graphical abstract

Review

Jump to: Research

Review
Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy
Int. J. Mol. Sci. 2020, 21(19), 7406; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197406 - 07 Oct 2020
Cited by 7 | Viewed by 1039
Abstract
Cardiovascular disease (CVD) comprises a range of major clinical cardiac and circulatory diseases, which produce immense health and economic burdens worldwide. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable [...] Read more.
Cardiovascular disease (CVD) comprises a range of major clinical cardiac and circulatory diseases, which produce immense health and economic burdens worldwide. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable to surgical revascularization. Therefore, more efficient therapeutic approaches are urgently required to promote neovascularization. Therapeutic angiogenesis represents an emerging strategy that aims at reconstructing the damaged vascular network by stimulating local angiogenesis and/or promoting de novo blood vessel formation according to a process known as vasculogenesis. In turn, circulating endothelial colony-forming cells (ECFCs) represent truly endothelial precursors, which display high clonogenic potential and have the documented ability to originate de novo blood vessels in vivo. Therefore, ECFCs are regarded as the most promising cellular candidate to promote therapeutic angiogenesis in patients suffering from CVD. The current briefly summarizes the available information about the origin and characterization of ECFCs and then widely illustrates the preclinical studies that assessed their regenerative efficacy in a variety of ischemic disorders, including acute myocardial infarction, peripheral artery disease, ischemic brain disease, and retinopathy. Then, we describe the most common pharmacological, genetic, and epigenetic strategies employed to enhance the vasoreparative potential of autologous ECFCs by manipulating crucial pro-angiogenic signaling pathways, e.g., extracellular-signal regulated kinase/Akt, phosphoinositide 3-kinase, and Ca2+ signaling. We conclude by discussing the possibility of targeting circulating ECFCs to rescue their dysfunctional phenotype and promote neovascularization in the presence of CVD. Full article
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Show Figures

Figure 1

Back to TopTop