Articular cartilage regeneration is a major challenge in orthopedic medicine. Endothelial progenitor cells (EPCs) are a promising cell source for regenerative medicine applications. However, their roles and functions in cartilage regeneration are not well understood. Additionally, thermosensitive chitosan hydrogels have been widely used in tissue engineering, but further development of these hydrogels incorporating vascular lineage cells for cartilage repair is insufficient. Thus, this study aimed to characterize the ability of EPCs to undergo endothelial-mesenchymal stem cell transdifferentiation and chondrogenic differentiation and investigate the ability of chondrogenic EPC-seeded thermosensitive chitosan-graft-poly (N-isopropylacrylamide) (CEPC-CSPN) scaffolds to improve healing in a rabbit osteochondral defect (OCD) model. EPCs were isolated and endothelial-to-mesenchymal transition (EndMT) was induced by transforming growth factor-β1 (TGF-β1); these EPCs are subsequently termed transdifferentiated EPCs (tEPCs). The stem cell-like properties and chondrogenic potential of tEPCs were evaluated by a series of in vitro assays. Furthermore, the effect of CEPC-CSPN scaffolds on OCD repair was evaluated. Our in vitro results confirmed that treatment of EPC with TGF-β1 induced EndMT and the acquisition of stem cell-like properties, producing tEPCs. Upon inducing chondrogenic differentiation of tEPCs (CEPCs), the cells exhibited significantly enhanced chondrogenesis and chondrocyte surface markers after 25 days. The TGF-β1-induced differentiation of EPCs is mediated by both the TGF-β/Smad and extracellular signal-regulated kinase (Erk) pathways. The CEPC-CSPN scaffold reconstructed well-integrated translucent cartilage and repaired subchondral bone in vivo, exhibiting regenerative capacity. Collectively, our results suggest that the CEPC-CSPN scaffold induces OCD repair, representing a promising approach to articular cartilage regeneration.

Congenital heart disease (CHD) can be complicated by pulmonary arterial hypertension (PAH). Cardiopulmonary bypass (CPB) for corrective surgery may cause endothelial dysfunction, involving endothelin-1 (ET-1), circulating endothelial cells (CECs), and endothelial progenitor cells (EPCs). These markers can gauge disease severity, but their levels in children\'s peripheral blood still lack consensus for prognostic value. The aim of our study was to investigate changes in ET-1, cytokines, and the absolute numbers (Ɲ) of CECs and EPCs in children 24 h before and 48 h after CPB surgery to identify high-risk patients of complications. A cohort of 56 children was included: 41 cases with CHD-PAH (22 with high pulmonary flow and 19 with low pulmonary flow) and 15 control cases. We observed that Ɲ-CECs increased in both CHD groups and that Ɲ-EPCs decreased in the immediate post-surgical period, and there was a strong negative correlation between ET-1 and CEC before surgery, along with significant changes in ET-1, IL8, IL6, and CEC levels. Our findings support the understanding of endothelial cell precursors\' role in endogenous repair and contribute to knowledge about endothelial dysfunction in CHD.

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 (EPCs) are stem cells that can repair injured blood vessels through neovascularisation. This is achieved through secretion of growth factors and endothelial maturation. EPC numbers and function have been studied to determine their diagnostic, prognostic and therapeutic potential in many ischaemic diseases such as stroke. However their activation homing and migration is not definitively understood in stroke patients. In this study, we profiled the non-stroke control group recruited into the Dunhill Medical Trust Endothelial Progenitor Cell Study. Demographic, clinical and plasma levels of angiogenic regulators of participants were analysed to determine if there was any correlation with EPC numbers, subtypes and function. Participants with diabetes had significantly supressed EPC numbers (CD45-CD34 + CD133 + KDR+) and CD34 + KDR + and KDR + EPC subtypes. Male participants had significantly lower EPC numbers compared to female participants and the proliferative capacity of endothelial colony forming cells significantly decreased with increasing participant age. Pro-angiogenic proteins such as granulocyte colony-stimulating factor and stromal cell-derived factor were positively correlated with both undifferentiated and endothelial-committed EPC subtype numbers (CD133+, KDR+, CD34 + CD133+, CD34 + KDR+), whereas anti-angiogenic proteins such as thrombospondin-1 showed a negative correlation with undifferentiated EPC subtypes (CD133+, CD34 + CD133+) but a positive correlation with endothelial-committed EPC subtype numbers (KDR+, CD34 + KDR+). These results show that EPC numbers and subtypes are affected by many factors and larger studies which can analyse and deconvolute the interactions between comorbidities, plasma biomarker levels and EPC are needed.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are prevalent and debilitating conditions with a significant impact on patients\' quality of life. In this study, we conducted a comprehensive investigation into the histological characteristics of renal progenitor/stem cells (RPCs), renal mesenchymal stem-like cells, and endothelial progenitor cells (EPCs) in CKD and ESRD patients. Additionally, we performed a molecular docking analysis to explore potential drug-receptor interactions involving common medications prescribed to CKD patients. Our histological examination revealed a noteworthy increase in the number of CD24- and CD133-positive cells in CKD and ESRD patients, representing RPCs. These cells are implicated in kidney repair and regeneration, underscoring their potential role in CKD management. Moreover, we observed an elevation in the number of EPCs within the kidneys of CKD and ESRD patients, suggesting a protective role of EPCs in kidney preservation. The molecular docking analysis unveiled intriguing insights into potential drug interventions. Notably, digoxin exhibited the highest in-silico binding affinity to numerous receptors associated with the functions of RPCs, renal mesenchymal stem-like cells, and EPCs, emphasizing the potential multifaceted effects of this cardiac glycoside in CKD patients. Other drugs, including apixaban, glimepiride, and glibenclamide, also displayed strong in-silico affinities to specific receptors, indicating their potential influence on various renal cell functions. In conclusion, this study provides valuable insights into the histological alterations in renal cell populations in CKD and ESRD patients and underscores the potential roles of RPCs and EPCs in kidney repair and preservation. The molecular docking analysis reveals the complex interactions between common drugs and renal cells, suggesting the need for further in-vitro and in-vivo research to fully understand these relationships. These findings contribute to our understanding of CKD and offer new avenues for research into potential therapeutic interventions.

Multiple myeloma (MM) is a prevalent yet incurable hematologic malignancy. Despite the proven efficacy of proteasome inhibitors in treating MM, resistance to Bortezomib-based treatments persists in a subset of patients. This case control study explores the potential of circulating endothelial progenitor cells (EPCs) as biomarkers for predicting response to Proteasome Inhibitor based therapy combined with Dexamethasone in MM patients. This study was conducted on 105 MM patients receiving bortezomib plus dexamethasone therapy and 90 healthy individuals as a control group. Utilizing 8-color multi-parameter flow cytometry, we assessed the levels of circulating EPCs, identified through CD34 FITC and CD309 PE markers at diagnosis and after one treatment cycle (4 weeks). Our findings revealed that patients exhibiting poor response to therapy showed significantly higher CD34/CD309 values than those with a good response (p < 0.001). The delineation of response based on CD34/CD309 expression was established with a cutoff ≤ 0.9 for percentage (yielding 100% sensitivity and 94.1% specificity) and ≤ 12.5 for absolute value (also with 100% sensitivity and 94.1% specificity). These results underscore the potential of EPC population levels, as quantified by CD34/CD309, to serve as a predictive biomarker for immunomodulatory treatment in MM patients undergoing Proteasome Inhibitor and Dexamethasone therapy.

Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.

UNASSIGNED: Venous leg ulcers (VLUs) are prevalent chronic wounds with limited treatment options. This study aimed to investigate the potential of berberine to enhance endothelial progenitor cell (EPC) function in VLU healing.
UNASSIGNED: Histopathological changes and inflammatory cytokine levels in a deep venous thrombosis (DVT) mouse model were assessed using HE staining and ELISA assays. A luciferase reporter assay was employed to identify the miR-21-3p and RRAGB targeting relationship. EPC proliferation, migration, and tube formation were evaluated through CCK-8, Transwell, and tubule formation assays, while the mTOR pathway and autophagy-related proteins were analyzed by immunofluorescence staining and western blotting.
UNASSIGNED: Berberine significantly improved EPC functions, such as proliferation, migration, and tube formation in vitro, and enhanced in vivo EPC-mediated wound healing in a DVT mouse model. Furthermore, miR-21-3p was downregulated in EPCs from VLU patients, and its overexpression improved model EPC functions. Mechanistically, RRAGB, which regulates the mTOR pathway, was identified as a potential miR-21-3p target in EPCs. Overexpression of RRAGB inhibited autophagic activity and impaired EPC function.
UNASSIGNED: Berberine shows promise in ameliorating EPC function and promoting wound healing in VLUs. The regulation of the miR-21-3p/RRAGB axis by berberine could offer a promising therapeutic approach for managing VLUs.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia, leading to various vascular complications. Accumulating evidence indicates that endothelial colony-forming cells (ECFCs) have attractive prospects for repairing and restoring blood vessels. Thus, ECFCs may be a novel therapeutic option for diabetic patients with vascular complications who require revascularization therapy. However, it has been reported that the function of ECFCs is impaired in DM, which poses challenges for the autologous transplantation of ECFCs. In this review, we summarize the molecular mechanisms that may be responsible for ECFC dysfunction and discuss potential strategies for improving the therapeutic efficacy of ECFCs derived from patients with DM. Finally, we discuss barriers to the use of ECFCs in human studies in light of the fact that there are no published reports using these cells in humans.

BACKGROUND: This study explores the potential role of Thioredoxin-interacting protein (TXNIP) silencing in endothelial colony-forming cells (ECFCs) within the scope of age-related comorbidities and impaired vascular repair. We aim to elucidate the effects of TXNIP silencing on vasculogenic properties, paracrine secretion, and neutrophil recruitment under conditions of metabolic stress.
METHODS: ECFCs, isolated from human blood cord, were transfected with TXNIP siRNA and exposed to a high glucose and β-hydroxybutyrate (BHB) medium to simulate metabolic stress. We evaluated the effects of TXNIP silencing on ECFCs\' functional and secretory responses under these conditions. Assessments included analyses of gene and protein expression profiles, vasculogenic properties, cytokine secretion and neutrophil recruitment both in vitro and in vivo. The in vivo effects were examined using a murine model of hindlimb ischemia to observe the physiological relevance of TXNIP modulation under metabolic disorders.
RESULTS: TXNIP silencing did not mitigate the adverse effects on cell recruitment, vasculogenic properties, or senescence induced by metabolic stress in ECFCs. However, it significantly reduced IL-8 secretion and consequent neutrophil recruitment under these conditions. In a mouse model of hindlimb ischemia, endothelial deletion of TXNIP reduced MIP-2 secretion and prevented increased neutrophil recruitment induced by age-related comorbidities.
CONCLUSIONS: Our findings suggest that targeting TXNIP in ECFCs may alleviate ischemic complications exacerbated by metabolic stress, offering potential clinical benefits for patients suffering from age-related comorbidities.