Recent advances in endothelial colony-forming cells: from the transcriptomic perspective.

Endothelial colony-forming cells (ECFCs) are progenitors of endothelial cells with significant proliferative and angiogenic ability. ECFCs are a promising treatment option for various diseases, such as ischemic heart disease and peripheral artery disease. However, some barriers hinder the clinical application of ECFC therapeutics. One of the current obstacles is that ECFCs are dysfunctional due to the underlying disease states. ECFCs exhibit dysfunctional phenotypes in pathologic states, which include but are not limited to the following: premature neonates and pregnancy-related diseases, diabetes mellitus, cancers, haematological system diseases, hypoxia, pulmonary arterial hypertension, coronary artery diseases, and other vascular diseases. Besides, ECFCs are heterogeneous among donors, tissue sources, and within cell subpopulations. Therefore, it is important to elucidate the underlying mechanisms of ECFC dysfunction and characterize their heterogeneity to enable clinical application. In this review, we summarize the current and potential application of transcriptomic analysis in the field of ECFC biology. Transcriptomic analysis is a powerful tool for exploring the key molecules and pathways involved in health and disease and can be used to characterize ECFC heterogeneity.

The Functionality of Endothelial-Colony-Forming Cells from Patients with Diabetes Mellitus.

Endothelial-colony-forming cells (ECFCs) are a population of progenitor cells which have demonstrated promising angiogenic potential both in vitro and in vivo. However, ECFCs from diabetic patients have been shown to be dysfunctional compared to ECFCs from healthy donors. Diabetes mellitus itself presents with many vascular co-morbidities and it has been hypothesized that ECFCs may be a potential cell therapy option to promote revascularisation in these disorders. While an allogeneic cell therapy approach would offer the potential of an 'off the shelf' therapeutic product, to date little research has been carried out on umbilical cord-ECFCs in diabetic models. Alternatively, autologous cell therapy using peripheral blood-ECFCs allows the development of a personalised therapeutic approach to medicine; however, autologous diabetic ECFCs are dysfunctional and need to be repaired so they can effectively treat diabetic co-morbidities. Many different groups have modified autologous diabetic ECFCs to improve their function using a variety of methods including pre-treatment with different factors or with genetic modification. While the in vitro and in vivo data from the literature is promising, no ECFC therapy has proceeded to clinical trials to date, indicating that more research is needed for a potential ECFC therapy in the future to treat diabetic complications.

Recent Advances in Endothelial Progenitor Cells Toward Their Use in Clinical Translation.

Since the discovery of Endothelial Progenitor Cells (EPC) by Asahara and colleagues in 1997, an increasing number of preclinical studies have shown that EPC based therapy is feasible, safe, and efficacious in multiple disease states. Subsequently, this has led to several, mainly early phase, clinical trials demonstrating the feasibility and safety profile of EPC therapy, with the suggestion of efficacy in several conditions including ischemic heart disease, pulmonary arterial hypertension and decompensated liver cirrhosis. Despite the use of the common term "EPC," the characteristics, manufacturing methods and subset of the cell type used in these studies often vary significantly, rendering clinical translation challenging. It has recently been acknowledged that the true EPC is the endothelial colony forming cells (ECFC). The objective of this review was to summarize and critically appraise the registered and published clinical studies using the term "EPC," which encompasses a heterogeneous cell population, as a therapeutic agent. Furthermore, the preclinical data using ECFC from the PubMed and Web of Science databases were searched and analyzed. We noted that despite the promising effect of ECFC on vascular regeneration, no clinical study has stemmed from these preclinical studies. We showed that there is a lack of information registered on www.clinicaltrials.gov for EPC clinical trials, specifically on cell culture methods. We also highlighted the importance of a detailed definition of the cell type used in EPC clinical trials to facilitate comparisons between trials and better understanding of the potential clinical benefit of EPC based therapy. We concluded our review by discussing the potential and limitations of EPC based therapy in clinical settings.