Abstract
IntroductionTransplantation of endothelial progenitor cells (EPCs) restores endothelial function in patients with endothelial dysfunction and initial denudation. The goal of the present study was to determine the effect of cryopreserved human umbilical cord blood (UCB)-derived EPC infusion on the repair of carotid artery injury in nude rats.MethodsMononuclear cells (MNCs) from human cryopreserved UCB and peripheral blood (PB) of patients with cardiovascular diseases and healthy volunteers were cultured in a conditioned medium. The in vitro migration, proliferation, adhesion, and survival capacities, as well as paracrine cytokine release of EPCs were investigated. EPC homing, induced reendothelialization, and the effect on neointima formation were also assessed in vivo.ResultsPatient-derived PB EPCs (PPB-EPCs) displayed decreased migration, proliferation, adhesion, and survival capabilities as compared to PB-EPCs from healthy volunteers (HPB-EPCs) and cryopreserved UCB-EPCs. However, there was no difference in the release of vascular endothelial growth factor (VEGF) and stromal cell derived factor 1 (SDF-1) between the three groups. Two weeks after transplantation, more labeled UCB-EPCs and HPB-EPCs than PPB-EPCs were found by cell tracking in the injury zone. Administration of PPB-EPCs, HPB-EPCs, and UCB-EPCs enhanced reendothelialization and inhibited neointima formation compared to the saline control. However, UCB-EPC and HPB-EPC infusion showed a greater improvement than PPB-EPCs.ConclusionsCryopreserved UCB-MNCs derived EPCs and HPB-EPCs show better responses to cytokines and vascular injury than PPB-EPCs. Thus, cryopreservation and delivery of cryopreserved autogenous UCB-EPCs or HPB-EPCs may be a promising vasculoprotective approach for patients with multiple cardiovascular risk factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0022-4) contains supplementary material, which is available to authorized users.
Highlights
Transplantation of endothelial progenitor cells (EPCs) restores endothelial function in patients with endothelial dysfunction and initial denudation
Previous experiments have suggested that endothelial progenitor cells (EPCs)—derived from hematopoietic stem cells (HSCs)—have the potential to incorporate into the site of vessel injury and differentiate into endothelial cells, thereby contributing to the improvement of endothelial function [2]
Characterization of cultured EPCs Cryopreserved umbilical cord blood (UCB)-Mononuclear cells (MNCs) cultured under endothelialspecific conditions developed into normal cell colonies by day 7 after isolation (Figure 1A)
Summary
Transplantation of endothelial progenitor cells (EPCs) restores endothelial function in patients with endothelial dysfunction and initial denudation. Previous experiments have suggested that endothelial progenitor cells (EPCs)—derived from hematopoietic stem cells (HSCs)—have the potential to incorporate into the site of vessel injury and differentiate into endothelial cells, thereby contributing to the improvement of endothelial function [2]. Growing evidence has shown that EPCs from patients with cardiovascular risk factors, including diabetes, hypertension, metabolic syndrome, smoking, aging, and coronary artery disease, or other diseases, such as emphysema, acute lung injury, liver fibrosis, and systemic sclerosis, are associated with decreased number and impaired function [4,5]. Umbilical cord blood (UCB) is a traditional source of HSCs for the treatment of various diseases beyond hematologic diseases such as Langerhans-cell histocytosis and Bare-lymphocyte syndrome. UCB has been shown to contain a large number of progenitors, and transplantation
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