Mobilization of endothelial precursor cells: Systemic vascular response to musculoskeletal trauma

Abstract

Postnatal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells (EPC) migrate, differentiate, and incorporate into the nacent endothelium contributing to physiological and pathological neovascularization, has stimulated much interest. Its contribution to tumor nonvascularization, wound healing, and revascularization associated with skeletal and cardiac muscles ischaemia is established. We evaluated the mobilization of EPCs in response to musculoskeletal trauma. Blood from patients (n ¼ 15) following AO type 42a1 closed diaphyseal tibial fractures was analyzed for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched CD34þ mononuclear cell (MNC CD34þ ) populations were cultured and examined for phenotypic and functional vascular endothelial differentiation. Circulating MNC CD34þ levels increased sevenfold by day 3 postinjury. Circulating MNC AC133þ increased 2.5-fold. Enriched MNC CD34þ populations from day 3 samples in culture exhibited cell cluster formation with sprouting spindles. These cells bound UEA-1 and incorporated fluorescent DiI-Ac-LDL intracellularily. Our findings suggest a systemic provascular response is initiated in response to musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of fracture healing. ß

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

“…While the higher vasculogenic potential of UCB-derived ECFC is largely expected, the higher expression of osteogenesis-related genes here may reflect the intense skeletal development occurring during neonatal life as compared to the mature adult. These circulating ECFC are found at higher frequencies during neonatal life compared to adult life [46], with increased mobilization in the event of bony injury [47,48].…”

Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study

“…We found the largest increase in EPCs at Day 7, which may indicate the true peak of EPC mobilization in our model was at an earlier time point. Increased endothelial precursor cells have also been observed after closed tibial fracture in patients [32]. Wang et al [57] reported a doubling in circulating HSCs at 7 days after creation of a calvarial defect in C57BL/6 male mice and this number was further increased when AMD3100 was administered.…”

“…This new paradigm uses pharmacologic induction of mobilization and endogenous mechanisms of cell homing and engraftment to sites of injury. It is plausible this strategy simply mimics and amplifies normal repair mechanisms as progenitor cells are mobilized to the PB after stroke [41], vascular trauma [20], musculoskeletal trauma [31,32], fracture [3,34], distraction osteogenesis [34], and myocardial infarction [60]. An important pathway for stem cell mobilization is the SDF-1/CXCR4 axis and there are recent data supporting the concept that transient disruption of this receptor-ligand complex through the CXCR4 antagonist, AMD3100, enhances bone formation in vivo [57,59].…”

Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients

“…22 There seem to be several distinct cell populations capable of giving rise to osteoblasts, 6,11,23 with CD34 expression as the only shared characteristic. In fracture patients, circulating non-adherent CD34+ preosteoblasts, 11 and fibronectin adherent CD34+ cells 23 have been found at elevated numbers. Also osteogenic differentiation of circulating EPCs has been demonstrated, and PB derived CD34+ cells have been shown to recruit to fracture sites when systemically injected in a rat model.…”