title: The Role of Endothelial Progenitor Cells in Postnatal Vasculogenesis: Implications for Therapeutic Neovascularization and Wound Healing.
abstract: CONCLUSIONS
  Postnatal vasculogenesis mediated via endothelial progenitor cells (EPCs) contributes to re-endothelialization and augments neovascularization after ischemia and tissue injury, providing a novel therapeutic application. However, controversy exists with respect to the origin, identification, and contributions of the EPCs to neovascularization, necessitating further study.
  
  
  BACKGROUND
  Bone marrow (BM) or circulating cells expressing cd133/vascular endothelial growth factor receptor 2 include those with endothelial progenitor capacity. Increasing evidence suggests that there are additional BM-derived (myeloid; mesenchymal cells) and non-BM-derived (peripheral and cord-blood; tissue-resident) cell populations which also give rise to endothelial cells (ECs) and contribute to re-endothelialization and growth factor release after ischemia and tissue injury. Currently, EPCs are being used as diagnostic markers for the assessment of cardiovascular and tumor risk/progression. Techniques aimed at enhancingex vivoexpansion and the therapeutic potential of these cells are being optimized.
  
  
  RESULTS
  Mobilization and EPC-mediated neovascularization are critically regulated. Stimulatory (growth factors, statins, and exercise) or inhibitory factors (obesity, diabetes, and other cardiovascular diseases) modulate EPC numbers and function. Recruitment and incorporation of EPCs require a coordinated sequence of signaling events, including adhesion, migration (by integrins), and chemoattraction. Finally, EPCs differentiate into ECs and/or secrete angiogenic growth factors. These cells are highly plastic, and depending on the microenvironment and presence of other cells, EPCs transdifferentiate and/or undergo cell fusion and become cells of a different lineage. Therefore,in vitroculture conditions should be optimized to mimic thein vivomilieu to fully characterize the biological function and contribution of EPCs to postnatal vasculogenesis.
  
  
  CONCLUSIONS
  Advances in characterization of the EPC biology and enhancement of EPC functions are required. In addition, innovative tissue-engineered carrier matrices that permit embedding of EPCs and provide optimal conditions for EPC survival and endothelial outgrowth will further contribute to EPC-mediated therapeutic applications in wound healing and ischemia repair.
authors: Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital and the University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors: Swathi
authors: S
authors: Balaji
authors: Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital and the University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors: Alice
authors: A
authors: King
authors: Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital and the University of Cincinnati College of Medicine , Cincinnati, Ohio. ; Center for Children's Surgery, Children's Hospital Colorado and the University of Colorado School of Medicine , Aurora, Colorado.
authors: Timothy M
authors: TM
authors: Crombleholme
authors: Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital and the University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors: Sundeep G
authors: SG
authors: Keswani