Role Of Endothelial Progenitor Cells Research Articles

Potential role of endothelial progenitor cells in the pathogenesis and treatment of cerebral aneurysm.

Cerebral aneurysm (CA) is a significant health concern that results from pathological dilations of blood vessels in the brain and can lead to severe and potentially life-threatening conditions. While the pathogenesis of CA is complex, emerging studies suggest that endothelial progenitor cells (EPCs) play a crucial role. In this paper, we conducted a comprehensive literature review to investigate the potential role of EPCs in the pathogenesis and treatment of CA. Current research indicates that a decreased count and dysfunction of EPCs disrupt the balance between endothelial dysfunction and repair, thus increasing the risk of CA formation. Reversing these EPCs abnormalities may reduce the progression of vascular degeneration after aneurysm induction, indicating EPCs as a promising target for developing new therapeutic strategies to facilitate CA repair. This has motivated researchers to develop novel treatment options, including drug applications, endovascular-combined and tissue engineering therapies. Although preclinical studies have shown promising results, there is still a considerable way to go before clinical translation and eventual benefits for patients. Nonetheless, these findings offer hope for improving the treatment and management of this condition.

Endothelial Progenitor Cells: A Review of Molecular Mechanisms in the Pathogenesis and Endovascular Treatment of Intracranial Aneurysms.

This comprehensive review explores the multifaceted role of endothelial progenitor cells (EPCs) in vascular diseases, focusing on their involvement in the pathogenesis and their contributions to enhancing the efficacy of endovascular treatments for intracranial aneurysms (IAs). Initially discovered as CD34+ bone marrow-derived cells implicated in angiogenesis, EPCs have been linked to vascular repair, vasculogenesis, and angiogenic microenvironments. The origin and differentiation of EPCs have been subject to debate, challenging the conventional notion of bone marrow origin. Quantification methods, including CD34+ , CD133+ , and various assays, reveal the influence of factors, like age, gender, and comorbidities on EPC levels. Cellular mechanisms highlight the interplay between bone marrow and angiogenic microenvironments, involving growth factors, matrix metalloproteinases, and signaling pathways, such as phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). In the context of the pathogenesis of IAs, EPCs play a role in maintaining vascular integrity by replacing injured and dysfunctional endothelial cells. Recent research has also suggested the therapeutic potential of EPCs after coil embolization and flow diversion, and this has led the development of device surface modifications aimed to enhance endothelialization. The comprehensive insights underscore the importance of further research on EPCs as both therapeutic targets and biomarkers in IAs.

Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

Pulmonary arterial hypertension in children with congenital heart disease: a deeper look into the role of endothelial progenitor cells and circulating endothelial cells to assess disease severity.

Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75-10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects.

Role of Endothelial Progenitor Cells in Frailty.

Frailty is a clinical condition closely related to aging which is characterized by a multidimensional decline in biological reserves, a failure of physiological mechanisms and vulnerability to minor stressors. Chronic inflammation, the impairment of endothelial function, age-related endocrine system modifications and immunosenescence are important mechanisms in the pathophysiology of frailty. Endothelial progenitor cells (EPCs) are considered important contributors of the endothelium homeostasis and turn-over. In the elderly, EPCs are impaired in terms of function, number and survival. In addition, the modification of EPCs' level and function has been widely demonstrated in atherosclerosis, hypertension and diabetes mellitus, which are the most common age-related diseases. The purpose of this review is to illustrate the role of EPCs in frailty. Initially, we describe the endothelial dysfunction in frailty, the response of EPCs to the endothelial dysfunction associated with frailty and, finally, interventions which may restore the EPCs expression and function in frail people.

Tm4sf1-marked Endothelial Subpopulation Is Dysregulated in Pulmonary Arterial Hypertension.

The identification and role of endothelial progenitor cells in pulmonary arterial hypertension (PAH) remain controversial. Single-cell omics analysis can shed light on endothelial progenitor cells and their potential contribution to PAH pathobiology. We aim to identify endothelial cells that may have stem/progenitor potential in rat lungs and assess their relevance to PAH. Differential expression, gene set enrichment, cell-cell communication, and trajectory reconstruction analyses were performed on lung endothelial cells from single-cell RNA sequencing of Sugen-hypoxia, monocrotaline, and control rats. Relevance to human PAH was assessed in multiple independent blood and lung transcriptomic data sets. Rat lung endothelial cells were visualized by immunofluorescence in situ, analyzed by flow cytometry, and assessed for tubulogenesis invitro. A subpopulation of endothelial cells (endothelial arterial type 2 [EA2]) marked by Tm4sf1 (transmembrane 4 L six family member 1), a gene strongly implicated in cancer, harbored a distinct transcriptomic signature enriched for angiogenesis and CXCL12 signaling. Trajectory analysis predicted that EA2 has a less differentiated state compared with other endothelial subpopulations. Analysis of independent data sets revealed that TM4SF1 is downregulated in lungs and endothelial cells from patients and PAH models, is a marker for hematopoietic stem cells, and is upregulated in PAH circulation. TM4SF1+CD31+ rat lung endothelial cells were visualized in distal pulmonary arteries, expressed hematopoietic marker CD45, and formed tubules in coculture with lung fibroblasts. Our study uncovered a novel Tm4sf1-marked subpopulation of rat lung endothelial cells that may have stem/progenitor potential and demonstrated its relevance to PAH. Future studies are warranted to further elucidate the role of EA2 and Tm4sf1 in PAH.

Restenosis after Coronary Stent Implantation: Cellular Mechanisms and Potential of Endothelial Progenitor Cells (A Short Guide for the Interventional Cardiologist).

Coronary stents are among the most common therapies worldwide. Despite significant improvements in the biocompatibility of these devices throughout the last decades, they are prone, in as many as 10–20% of cases, to short- or long-term failure. In-stent restenosis is a multifactorial process with a complex and incompletely understood pathophysiology in which inflammatory reactions are of central importance. This review provides a short overview for the clinician on the cellular types responsible for restenosis with a focus on the role of endothelial progenitor cells. The mechanisms of restenosis are described, along with the cell-based attempts made to prevent it. While the focus of this review is principally clinical, experimental evidence provides some insight into the potential implications for prevention and therapy of coronary stent restenosis.

A Review Into the Insights of the Role of Endothelial Progenitor Cells on Bone Biology.

In addition to its important transport functions, the skeletal system is involved in complex biological activities for the regulation of blood vessels. Endothelial progenitor cells (EPCs), as stem cells of endothelial cells (ECs), possess an effective proliferative capacity and a powerful angiogenic capacity prior to their differentiation. They demonstrate synergistic effects to promote bone regeneration and vascularization more effectively by co-culturing with multiple cells. EPCs demonstrate a significant therapeutic potential for the treatment of various bone diseases by secreting a combination of growth factors, regulating cellular functions, and promoting bone regeneration. In this review, we retrospect the definition and properties of EPCs, their interaction with mesenchymal stem cells, ECs, smooth muscle cells, and immune cells in bone regeneration, vascularization, and immunity, summarizing their mechanism of action and contribution to bone biology. Additionally, we generalized their role and potential mechanisms in the treatment of various bone diseases, possibly indicating their clinical application.

Endothelial Progenitor Cells in Coronary Artery Disease: From Bench to Bedside.

Endothelial progenitor cells (EPCs) are a heterogeneous group of cells present in peripheral blood at various stages of endothelial differentiation. EPCs have been extensively investigated in patients with coronary artery disease (CAD), with controversial findings both on their role in atherosclerosis progression and in the process of neointimal growth after a percutaneous coronary intervention (PCI). Despite nearly 2 decades of experimental and clinical investigations, however, the significance of EPCs in clinical practice remains unclear and poorly understood. This review provides an update on the role of EPCs in the most common clinical scenarios that are experienced by cardiologists managing patients with CAD. We here summarize the main findings on the association of EPCs with cardiovascular risk factors, coronary atherosclerosis, and myocardial ischemia. We then discuss the potential effects of EPCs in post-PCI in-stent restenosis, as well as most recent findings with EPC-coated stents. Based on the mounting evidence of the relationship between levels of EPCs and several different adverse cardiovascular events, EPCs are emerging as novel predictive biomarkers of long-term outcomes in patients with CAD.

The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair.

Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology.

Endothelial Progenitor Cells in Coronary Atherosclerosis and Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

IntroductionThe role of endothelial progenitor cells (EPCs) in atherosclerosis progression and neointimal growth after percutaneous coronary intervention (PCI) remains controversial. The purpose of this study was to perform a systematic review and meta-analysis of studies on EPCs in patients who had PCI. MethodsWe searched Pubmed, Embase and Cochrane databases and reviewed cited references up to August 31, 2021. Overall, we selected 9 studies, including 4612 patients. ResultsLower baseline EPC count was associated with a significantly greater occurrence of in-stent restenosis (HR 1.33; 95% CI 0.97–1.82, P = 0.045). As for EPC coating, there was no significant difference in the 1-year occurrence of cardiac death between EPCs-capturing drug-eluting stents (DES) and standard DES (Relative Risk [RR] 1.146; 95% CI 0.666–1.974, P = 0.98), but target lesion revascularization (RR 1.727; 95% CI: 1.199–2.487, P = 0.025), and target vessel failure (RR 1.591; 95% CI 1.213–2.088, P = 0.04) were significantly more common with EPCs-capturing DES than with standard DES. ConclusionCirculating EPC count might improve risk stratification after PCI, as it is correlated with the occurrence of in-stent restenosis. Currently available EPCs-capturing DES use was associated with an increased risk of 1-year adverse events, mainly driven by an increase in target lesion revascularization and target vessel failure, not cardiac death.

Long noncoding RNA p21 enhances autophagy to alleviate endothelial progenitor cells damage and promote endothelial repair in hypertension through SESN2/AMPK/TSC2 pathway

Vascular damage of hypertension has been the focus of hypertension treatment, and endothelial progenitor cells (EPCs) play an important role in the repair of vascular endothelial damage. Functional damage and decreased number of EPCs are observed in the peripheral circulation of hypertensive patients, but its mechanism is not yet elucidated. Here, we show that the number of EPCs in hypertensive patients is significantly lower than that of normal population, and the cell function decreases with a higher proportion of EPCs at later stages. A decrease in autophagy is responsible for the senescence and damage of EPCs induced by AngII. Moreover, lncRNA-p21 plays a critical regulator role in EPCs’ senescence and dysfunction. Furthermore, lncRNA-p21 activates SESN2/AMPK/TSC2 pathway by promoting the transcriptional activity of p53 and enhances autophagy to protect against AngII-induced EPC damage. The data provide evidence that a reversal of decreased autophagy serves as the protective mechanism of EPC injury in hypertensive patients, and lncRNA-p21 is a new therapeutic target for vascular endothelial repair in hypertension.

Endothelial Progenitor Cells: Relevant Players in the Vasculopathy and Lung Fibrosis Associated with the Presence of Interstitial Lung Disease in Systemic Sclerosis Patients.

Endothelial progenitor cells (EPC), which are key effectors in the physiologic vascular network, have been described as relevant players in autoimmune diseases. We previously showed that EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients. Given that ILD constitutes the main cause of mortality in systemic sclerosis (SSc) patients, we aimed to determine the EPC contribution to the pathogenic processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC quantification was performed by flow cytometry on blood from 83 individuals: 21 SSc-ILD+ patients and subjects from comparative groups (20 SSc-ILD− and 21 idiopathic pulmonary fibrosis (IPF) patients and 21 healthy controls (HC)). EPC were considered as CD34+, CD45low, CD309+, and CD133+. A significant increase in EPC frequency was found in SSc-ILD+ patients when compared to HC (p < 0.001). SSc-ILD+ patients exhibited a higher EPC frequency than SSc-ILD− patients (p = 0.012), whereas it was markedly reduced compared to IPF patients (p < 0.001). EPC frequency was higher in males (p = 0.04) and negatively correlated to SSc duration (p = 0.04) in SSc-ILD+ patients. Our results indicate a role of EPC in the processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC frequency may be considered as a biomarker of ILD in SSc patients.

The Role of Endothelial Progenitor Cells in Coronary Artery Disease: Basic Molecular Mechanisms and Its Clinical Potentials

BACKGROUND: Coronary artery disease (CAD) remains as the world number one cause of morbidity and mortality. Endothelial progenitor cells (EPCs) are known to be involved in vascular biology. Current review briefly summarizes the basics of EPCs and its clinical use in CAD.CONTENT: EPCs were firstly isolated in 1997 and involved in neovascularization. Further evidence defined EPCs into two distinguishable groups, namely: myeloid angiogenic cells (MACs) and endothelial colony forming cells (ECFCs). Common cardiovascular drugs, statin, angiotensin-converting enzyme (ACE) inhibitor, and their combinations, showed beneficial effects on EPCs. Likewise, the incorporation of EPCs upon CAD intervention management had been recently studied. Intramyocardial EPCs implementation and anti-CD34 antibody-coated stents could provide a promising option for refractory symptoms in CAD.SUMMARY: Association between EPCs and CAD is very dynamic and complex. EPCs could serve as both therapeutic target and agent in CAD patients. Subsequently, a universal definition of EPCs is needed for greater research in the future.KEYWORDS: atherosclerosis, coronary artery disease, endothelial progenitor cells, neovascularization

Association of Angiogenic Cells in the Tumour Microenvironment and the Circulating Matured Endothelial Cells in Astrocytic Glioma

Introduction: Astrocytic gliomas are the most common and lethal intracranial brain tumours and rely on angiogenesis for the tumour development. Endothelial progenitor cells (EPCs) contribute to the angiogenesis of glioma tumour. Objectives: The study aimed to investigate the matured circulating endothelial cells population in the peripheral blood mononuclear cells (PBMCs) and its associations with tissue resident angiogenic cells in astrocytic glioma patients. Methods: A total of 22 astrocytic glioma patients were recruited from Hospital Universiti Sains Malaysia. Tumour were sliced and stained with CD133+ and VEGFA+ for angiogenic cells (n=22). The circulating (CD133-/VEGFR2+) matured endothelial cells in PBMCs (n=22) were quantified using FACS. The paired t-test and Pearson correlation test were used for the data analysis. Results: The angiogenic cells in brain tumour tissue were significantly higher compared to adjacent normal brain tissue (median 1.07±0.96% vs. median 0.69±0.68%; Wilcoxon signed rank test Z=-3.100; p=0.002). Positive correlation was found between the angiogenic cells of brain tumour tissue and adjacent normal brain tissue (Spearman’s rho correlation test, r=0.56; p=0.007). Significant positive correlation was found between matured endothelial cells in peripheral circulating systems and angiogenic cells in tumour of astrocytic glioma patients (Pearson correlation test, r=0.60, p=0.003).Conclusion:The findings of the study give support to the possible roles of EPCs in astrocytic glioma patients. Thus targeting tissue resident angiogenic cells and matured circulating endothelial cells by antiangiogenic treatment might be useful to prevent the tumour growth.

Improved placental vascular repair in a rat preeclampsia model by implantation of endothelial progenitor cells treated with platelet microparticles

ABSTRACT Objective: To detect the role of endothelial progenitor cells (EPCs) treated with platelet microparticles (PMPs) in preeclampsia. Methods: EPCs treated with/without PMPs were labeled and injected to PE rats. The differentiation of EPCs, the change of endothelial nitric oxide synthase (eNOS), blood pressure and proteinuria were measured. The blood pressure and proteinuria increased in each of PE groups, and were improved by EPCs which was strengthened by PMPs. Transplantation of EPCs increased placental angiogenesis. The trend of change of NO was the same as blood pressure. Conclusion: Transplantation of EPCs treated with PMPs improved blood pressure and proteinuria more effectively.

Erythropoietin Preconditioning Mobilizes Endothelial Progenitor Cells to Attenuate Nephron-Sparing Surgery-Induced Ischemia-Reperfusion Injury

The purpose of this study was to examine the role of endothelial progenitor cells (EPCs) in protection against ischemic-reperfusion injury (IRI) in a nephron-sparing surgery (NSS) rat model using erythropoietin (EPO) preconditioning. Fifty-four male Sprague-Dawley rats were randomly divided into 3 groups for right kidney nephrectomy treatment: sham group (exposure without clamp treatment), NSS group (3 days of peritoneal phosphate buffered saline [PBS] injection before renal blood vessels were clamped for 40 mins and NSS was performed), and EPO group (3 days of EPO abdomen injections prior to renal blood vessel clamping for 40 min before NSS was performed). After 12, 24, and 72 hours, inferior vena cava blood and renal tissues were harvested. The extent of renal injury was assessed, along with EPC number, cell proliferation, angiogenesis, and vascular growth factor expression. EPO preconditioning significantly improved renal function and histologic morphology, indicated by reduced blood urea nitrogen (BUN) ([33.12 ± 1.88] vs [16.03 ± 0.91], P < .05) and serum creatinine (Scr) ([190.2 ± 20.23] vs [77.23 ± 5.82], P < .05) levels and histologic injury scores ([3.20 ± 0.78] vs [1.70 ± 0.67], P < .05). Angiogenesis in peritubular capillaries markedly increased in the EPO group. EPC numbers increased in the kidneys at 24 hours following reperfusion in the EPO group, compared to the NSS group. Furthermore, EPO preconditioning also increased SDF-1α and CXCR7 expression at 24 hours following reperfusion relative to the NSS group. These findings suggest that EPO pretreatment can reduce renal injury in rats caused by IRI. Mechanistically, this may be related to EPC mobilization and recruitment to injured renal tissues by SDF-1α and CXCR7.

Role of endothelial progenitor cells in vascular development, homestatic maintenance of blood vessels and in injury-mediated reparative response

Role of endothelial progenitor cells in vascular development, homestatic maintenance of blood vessels and in injury-mediated reparative response

MiR-9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway.

Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for thrombi recanalization. However, this role of EPCs is confined by some detrimental factors. The aim of this study was to explore the role of the miR‐9‐5p in regulation of the proliferation, migration and angiogenesis of EPCs and the subsequent therapeutic role in thrombosis event. Wound healing, transwell assay, tube formation assay and in vivo angiogenesis assay were carried out to measure cell migration, invasion and angiogenic abilities, respectively. Western blot was performed to elucidate the relationship between miR‐9‐5p and TRPM7 in the autophagy pathway. It was found that miR‐9‐5p could promote migration, invasion and angiogenesis of EPCs by attenuating TRPM7 expression via activating PI3K/Akt/autophagy pathway. In conclusion, miR‐9‐5p, targets TRPM7 via the PI3K/Ak/autophagy pathway, thereby mediating cell proliferation, migration and angiogenesis in EPCs. Acting as a potential therapeutic target, miR‐9‐5p may play an important role in the prognosis of DVT.

Cardioprotective Potential of Human Endothelial-Colony Forming Cells from Diabetic and Nondiabetic Donors.

Objective: The potential therapeutic role of endothelial progenitor cells (EPCs) in ischemic heart disease for myocardial repair and regeneration is subject to intense investigation. The aim of the study was to investigate the proregenerative potential of human endothelial colony-forming cells (huECFCs), a very homogenous and highly proliferative endothelial progenitor cell subpopulation, in a myocardial infarction (MI) model of severe combined immunodeficiency (SCID) mice. Methods: CD34+ peripheral blood mononuclear cells were isolated from patient blood samples using immunomagnetic beads. For generating ECFCs, CD34+ cells were plated on fibronectin-coated dishes and were expanded by culture in endothelial-specific cell medium. Either huECFCs (5 × 105) or control medium were injected into the peri-infarct region after surgical MI induction in SCID/beige mice. Hemodynamic function was assessed invasively by conductance micromanometry 30 days post-MI. Hearts of sacrificed animals were analyzed by immunohistochemistry to assess cell fate, infarct size, and neovascularization (huECFCs n = 15 vs. control n = 10). Flow-cytometric analysis of enzymatically digested whole heart tissue was used to analyze different subsets of migrated CD34+/CD45+ peripheral mononuclear cells as well as CD34−/CD45− cardiac-resident stem cells two days post-MI (huECFCs n = 10 vs. control n = 6). Results: Transplantation of human ECFCs after MI improved left ventricular (LV) function at day 30 post-MI (LVEF: 30.43 ± 1.20% vs. 22.61 ± 1.73%, p < 0.001; ΔP/ΔTmax 5202.28 ± 316.68 mmHg/s vs. 3896.24 ± 534.95 mmHg/s, p < 0.05) when compared to controls. In addition, a significantly reduced infarct size (50.3 ± 4.5% vs. 66.1 ± 4.3%, p < 0.05) was seen in huECFC treated animals compared to controls. Immunohistochemistry failed to show integration and survival of transplanted cells. However, anti-CD31 immunohistochemistry demonstrated an increased vascular density within the infarct border zone (8.6 ± 0.4 CD31+ capillaries per HPF vs. 6.2 ± 0.5 CD31+ capillaries per HPF, p < 0.001). Flow cytometry at day two post-MI showed a trend towards increased myocardial homing of CD45+/CD34+ mononuclear cells (1.1 ± 0.3% vs. 0.7 ± 0.1%, p = 0.2). Interestingly, we detected a significant increase in the population of CD34−/CD45−/Sca1+ cardiac resident stem cells (11.7 ± 1.7% vs. 4.7 ± 1.7%, p < 0.01). In a subgroup analysis no significant differences were seen in the cardioprotective effects of huECFCs derived from diabetic or nondiabetic patients. Conclusions: In a murine model of myocardial infarction in SCID mice, transplantation of huECFCs ameliorated myocardial function by attenuation of adverse post-MI remodeling, presumably through paracrine effects. Cardiac repair is enhanced by increasing myocardial neovascularization and the pool of Sca1+ cardiac resident stem cells. The use of huECFCs for treating ischemic heart disease warrants further investigation.