Topical Erythropoietin Accelerates Wound Closure in Patients with Diabetic Foot Ulcers: A Prospective, Multicenter, Single-Blind, Randomized, Controlled Trial.

The diabetic foot ulcer (DFU) is a major disabling complication of diabetes mellitus. Growing evidence suggests that topical erythropoietin (EPO) can promote wound healing. The aim of this study is to clinically assess the efficacy of a proprietary topical EPO-containing hydrogel for treating DFUs.

Interim Results of the Remede d'Or Study: A Multicenter, Single-Blind, Randomized, Controlled Trial to Assess the Safety and Efficacy of an Innovative Topical Formulation of Erythropoietin for Treating Diabetic Foot Ulcers.

To inform on the interim results of the Remede d'Or study, which is a prospective, multicenter, single-blind, randomized, controlled clinical study on the safety and efficacy of RMD-G1, a topical carbopol-based hydrogel with a fibronectin matrix whose active pharmaceutical ingredient is erythropoietin (EPO), for treating diabetic foot ulcers (DFU). The trial will comprise 20 patients with type 2 diabetes mellitus with neuroischemic DFUs who will be randomized into two groups: (1) a control group in which standard-of-care (SOC) will be used to treat the DFUs, and (2) a test group in which SOC and RMD-G1 will be used to treat the DFUs. On day 0, all participants will be randomized to receive either RMD-G1 and SOC treatment or SOC alone.

Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism.

We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing.

Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus.

Developing a new drug is expensive: the cost of going from bench to bedside is about $US1 billion. Therefore, the repurposing of an approved drug is potentially rewarding because it expands the drug's existing therapeutic profile and preempts additional development costs. As the safety profile of a repurposed drug is already well known, any new investigations could then focus on its efficacy and other therapeutic benefits.

The chemokine stromal cell-derived factor-1α promotes endothelial progenitor cell-mediated neovascularization of human transplanted fat tissue in diabetic immunocompromised mice.

Background: Stromal cell-derived factor-1α is a chemokine and mediates endothelial progenitor cell-induced neovascularization. Because vascularization of a graft is crucial for its survival, the authors investigated whether stromal cell-derived factor-1α could improve fat graft survival by inducing endothelial progenitor cell-mediated neovascularization and preventing its resorption.

Methods: The authors injected 1 ml of human fat tissue into the scalps of 30 diabetic and 10 nondiabetic immunocompromised mice.

Treating fat grafts with human endothelial progenitor cells promotes their vascularization and improves their survival in diabetes mellitus.

Background: Bone marrow-derived endothelial progenitor cells are required for vascularization of a fat graft to form a functional microvasculature within the graft and to facilitate its integration into the surrounding tissues. Organ transplantation carries a high risk of graft loss and rejection in patients with diabetes mellitus because endothelial progenitor cell function is impaired. The authors investigated the influence of endothelial progenitor cell treatment on the phenotype and survival of human fat grafts in immunocompromised mice with experimentally induced diabetes mellitus.

Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice.

Diabetes mellitus disrupts all phases of the wound repair cascade and leads to development of chronic wounds. We previously showed that topical erythropoietin (EPO) can promote wound repair in diabetic rats. Fibronectin (FN) has a critical role throughout the process of wound healing, yet it is deficient in wound tissues of diabetic patients.

Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2.

Diabetes mellitus type-2 (DM-2) contributes to atherogenesis by inducing endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In DM-2, the circulating EPC count is low and their functionality is impaired.

Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

Background: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice.

Red wine consumption improves in vitro migration of endothelial progenitor cells in young, healthy individuals.

Background: Endothelial progenitor cells (EPCs) contribute to the maintenance of vascular endothelial function. The moderate consumption of red wine provides cardiovascular protection.

Objective: We investigated the underlying molecular mechanism of EPC migration in young, healthy individuals who drank red wine.

Hyperglycemia and oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus.

Introduction: Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1alpha (SDF1alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway.

Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus.

Background: The function of endothelial progenitor cells (EPCs), which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O2-).

Topical erythropoietin promotes wound repair in diabetic rats.

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats.

Role of protein kinase C in the expression of endothelin converting enzyme-1.

Increased expression of endothelin converting enzyme-1 (ECE-1) is associated with diabetic nephropathy. The molecular mechanisms underlying this association, as yet unknown, possibly involve protein kinase C (PKC) pathways. In the present study, we examined the effects of high glucose and PKC activation on ECE-1 expression in primary human umbilical vein endothelial cells (HUVECs) and in HUVEC line (EA.

[Endothelial progenitor cells and atherosclerosis].

The integrity and functional activity of the endothelial monolayer play a crucial role in the prevention of atherosclerosis. Extended endothelial cell damage by cardiovascular risk factors can result in endothelial cell apoptosis with loss of the integrity of the endothelium. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels.

Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy.

Aims: Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Dox-induced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction.

Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner.

Objectives: Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Treatment with erythropoietin (Epo) has shown promise in CHF patients, yet its mechanisms of action remain elusive. Endothelial progenitor cells (EPC) contribute to postnatal angiogenesis and vasculogenesis, and Epo was shown to promote EPC mobilization.