Ex vivo nanofiber expansion and genetic modification of human cord blood-derived progenitor/stem cells enhances vasculogenesis.
The stem cell therapy for treating ischemic diseases is promising; however, the limited availability and compromised quality of progenitor cells in aged and diseased patients limit its therapeutic use. Here we report a nanofiber-based ex vivo stem cell expansion technology and proangiogenic growth factors overexpression of human umbilical cord blood (UCB)-derived progenitor cells to enhance angiogenic potential of therapeutic stem cells. The progenitor cells were expanded approximately 225-fold on nanofiber-based serum-free ex vivo expansion culture technique without inducing differentiation. The expanded cells express high levels of stem cell homing receptor, CXCR4, and adhesion molecule, LFA-1. The nanofiber-expanded stem cells uptake AcLDL effectively, and migrate efficiently in an in vitro transmigration assay. These expanded cells can also differentiate into endothelial and smooth muscle cells in vitro. In a NOD/SCID mouse hind limb vascular injury model, nanofiber-expanded cells were more effective in blood flow restoration and this effect was further augmented by VEGF(164) and PDGF-BB, growth factor overexpression. The data indicate that nanofiber-based ex vivo expansion technology can provide an essential number of therapeutic stem cells. Additionally, proangiogenic growth factors overexpression in progenitor cells can potentially improve autologous or allogeneic stem cell therapy for ischemic diseases.
Das
Hiranmoy
H
Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA. hiranmoy.das@osumc.edu
Abdulhameed
Nasreen
N
Joseph
Matthew
M
Sakthivel
Ramasamy
R
Mao
Hai-Quan
HQ
Pompili
Vincent J
VJ
D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D049329:Nanostructures; D018919:Neovascularization, Physiologic; D038081:Organogenesis; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A