Type-2 pericytes participate in normal and tumoral angiogenesis.
Tissue growth and function depend on vascularization, and vascular insufficiency or excess exacerbates many human diseases. Identification of the biological processes involved in angiogenesis will dictate strategies to modulate reduced or excessive vessel formation. We examine the essential role of pericytes. Their heterogeneous morphology, distribution, origins, and physiology have been described. Using double-transgenic Nestin-GFP/NG2-DsRed mice, we identified two pericyte subsets. We found that Nestin-GFP(-)/NG2-DsRed(+) (type-1) and Nestin-GFP(+)/NG2-DsRed(+) (type-2) pericytes attach to the walls of small and large blood vessels in vivo; in vitro, type-2, but not type-1, pericytes spark endothelial cells to form new vessels. Matrigel assay showed that only type-2 pericytes participate in normal angiogenesis. Moreover, when cancer cells were transplanted into Nestin-GFP/NG2-DsRed mice, type-1 pericytes did not penetrate the tumor, while type-2 pericytes were recruited during its angiogenesis. As inhibition of angiogenesis is a promising strategy in cancer therapy, type-2 pericytes may provide a cellular target susceptible to signaling and pharmacological manipulation in treating malignancy. This work also reports the potential of type-2 pericytes to improve blood perfusion in ischemic hindlimbs, indicating their potential for treating ischemic illnesses.
Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina; Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, North Carolina;
Alexander
A
Birbrair
Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
Tan
T
Zhang
Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
Zhong-Min
ZM
Wang
Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
Maria Laura
ML
Messi
Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina; and.
John D
JD
Olson
Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina; and Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Akiva
A
Mintz
Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina; Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, North Carolina; odelbono@wakehealth.edu.
Osvaldo
O
Delbono
D000199:Actins / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000098:blood supply*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006614:Hindlimb; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D064231:Nestin / Q000235:genetics; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000235:genetics; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D000199:Actins; D000941:Antigens; D015415:Biomarkers; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D064231:Nestin; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C413663:fluorescent protein 583
angiogenesis; pericytes; stem cells; tumor