CD34 Hybrid Cells Promote Endothelial Colony-Forming Cell Bioactivity and Therapeutic Potential for Ischemic Diseases

Abstract

Objective-Although endothelial progenitor cells (EPCs) have been reported to promote neovessel formation during vascular injury, the function of supporting cells of EPCs and their interaction with EPCs during EPC isolation remain unclear. Approach and Results-We investigated the functional properties of 2 types of EPCs, also known as endothelial colonyforming cells (ECFCs), CD34− /CD34 + cell-derived ECFCs (hybrid-dECFCs) and CD34 + cell-derived ECFCs (stemdECFCs), isolated using different methods, to elucidate the role of CD34− cell populations as cell-supporting niches. Using EPC colony-forming and insert coculture assays, we found that CD34 − accessory cells dynamically modulate hematopoietic stem cell-derived endothelial cell progenitor commitment via angiogenic cytokines secreted by CD34 − / CD11b + macrophages. On the basis of these findings, we isolated 2 types of ECFCs and investigated their bioactivities. We found that stem-dECFCs showed remarkably retarded cell growth, enhanced senescence, and decreased characteristics of ECFCs, whereas hybrid-dECFCs showed greater proliferative properties but delayed senescence. In a murine hindlimb ischemia model, hybrid-dECFCs showed significantly enhanced blood perfusion, capillary density, transplanted cell survival and proliferation, and angiogenic cytokine secretion compared with stem-dECFCs. In particular, the migratory capacity of hybrid-dECFCs was significantly enhanced, in part mediated via an augmented phosphorylation cascade of focal adhesion kinase and Src, resulting in a highly increased incorporation capacity of hybrid-dECFCs compared with stem-dECFCs. CD34− accessory cells of hybrid-dECFCs might be niche-supporting cells that facilitate cell survival, increase the secretion of angiogenic cytokines, and increase incorporation. Conclusions-This study provided important insight into blood vessel formation and repair in ischemic diseases

Vascular Regeneration by Stem/Progenitor Cells

“…20 In recent years, several groups have reported the effects of various genes and proteins on the function, differentiation, and migration of circulating progenitor cells both in vivo and in vitro. 21,22 For instance, bone marrow protein 9, a member of the transforming growth factor-β family, has been indicated to contribute to the differentiation of the endothelial progenitor cells. 23 The expression of bone marrow protein 9 and its receptor, activin receptor-like kinase 1, was greatly altered during the differentiation of these progenitor cells.…”

Thickness-controllable electrospun fibers promote tubular structure formation by endothelial progenitor cells

“…EPCs were isolated from human umbilical cord blood 26,27 obtained from donors at Pusan National University Hospital (PNUH, Yangsan, South Korea). All procedures were as described in a protocol approved by the Institutional Review Board of PNUH (Approval No.…”

“…The cells were still healthy and continued to proliferate at passage 6 and above. 26,27 spheroid culture of ePcs…”

Regenerative Principles Enrich Cardiac Rehabilitation Practice

“…30 Accordingly, early application of this cell population was made in patients with critical limb ischemia and was shown to impart benefit on the risk of amputation. 31,32 Furthermore, in patients with angina refractory to medical therapy, the CD34 + population has been implanted, providing initial evidence for diminished frequency of angina noted. 33-35 This was more formally evaluated in the ACT34-CMI trial that demonstrated evidence for improvement in exercise performance.…”