Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration.
Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration.
1 Center for Craniofacial Regeneration, Columbia University Medical Center , New York, New York.|2 Department of General Dentistry, Capital Medical University School of Stomatology , Beijing, China .
Jian
J
Zhou
3 Department of Internal Medicine and the Cancer Research and Treatment Center, University of New Mexico Health Science Center , Albuquerque, New Mexico.
Jason H
JH
Rogers
4 Pratt School of Engineering, Duke University , Durham, North Carolina.
Scott H
SH
Lee
5 W. M. Keck Center for Collaborative Neuroscience, Rutgers University , New Brunswick, New Jersey.
DongMing
D
Sun
6 Clemson-MUSC Bioengineering Program , Department of Craniofacial Biology, Charleston, South Carolina.
Hai
H
Yao
1 Center for Craniofacial Regeneration, Columbia University Medical Center , New York, New York.
Jeremy J
JJ
Mao
1 Center for Craniofacial Regeneration, Columbia University Medical Center , New York, New York.|7 Hematology/Oncology Division, Department of Medicine, University of Florida , Gainesville, Florida.
Kimi Y
KY
Kong
D000818:Animals; D001011:Aorta / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D007797:Laminin / Q000494:pharmacology; D008819:Mice, Nude; D009061:Mouth Mucosa / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011509:Proteoglycans / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012038:Regeneration / Q000187:drug effects
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
angiogenesis; endothelial progenitor cells; oral mucosa; postnatal endothelial cells