Jamie N Mayo1, Shawn E Bearden1,2. 1. Department of Biological Sciences, Idaho State University, Pocatello, Idaho, USA. 2. ISU Biomedical Research Institute, Idaho State University, Pocatello, Idaho, USA.
Abstract
OBJECTIVES: The mechanisms involved in activating pericytes, cells that ensheath capillaries, to engage in the formation of new capillaries, angiogenesis, remain unknown. In this study, the hypothesis was tested that pericytes could be stimulated to promote angiogenesis by driving the HIF pathway. METHODS: Pericytes were stimulated with CoCl2 to activate the HIF pathway. Stimulated pericytes were cocultured with endothelial cells in a wound healing assay and in a 3D collagen matrix assay of angiogenesis. A culture system of spinal cord tissue was used to assess microvascular outcomes after treatment with stimulated pericytes. Pharmaceutical inhibition of exosome production was also performed. RESULTS: Treatment with stimulated pericytes resulted in faster wound healing (1.92 ± 0.18 fold increase, p < 0.05), greater endothelial cord formation (2.9 ± 0.14 fold increase, p < 0.05) in cell culture assays, and greater vascular density (1.78 ± 0.23 fold increase, p < 0.05) in spinal cord tissue. Exosome secretion and the physical presence of stimulated pericytes were necessary in the promotion of angiogenic outcomes. CONCLUSIONS: These results elucidate a mechanism that may be exploited to enhance features of angiogenesis in the CNS.
OBJECTIVES: The mechanisms involved in activating pericytes, cells that ensheath capillaries, to engage in the formation of new capillaries, angiogenesis, remain unknown. In this study, the hypothesis was tested that pericytes could be stimulated to promote angiogenesis by driving the HIF pathway. METHODS: Pericytes were stimulated with CoCl2 to activate the HIF pathway. Stimulated pericytes were cocultured with endothelial cells in a wound healing assay and in a 3D collagen matrix assay of angiogenesis. A culture system of spinal cord tissue was used to assess microvascular outcomes after treatment with stimulated pericytes. Pharmaceutical inhibition of exosome production was also performed. RESULTS: Treatment with stimulated pericytes resulted in faster wound healing (1.92 ± 0.18 fold increase, p < 0.05), greater endothelial cord formation (2.9 ± 0.14 fold increase, p < 0.05) in cell culture assays, and greater vascular density (1.78 ± 0.23 fold increase, p < 0.05) in spinal cord tissue. Exosome secretion and the physical presence of stimulated pericytes were necessary in the promotion of angiogenic outcomes. CONCLUSIONS: These results elucidate a mechanism that may be exploited to enhance features of angiogenesis in the CNS.
Authors: Bas W M van Balkom; Olivier G de Jong; Michiel Smits; Jolanda Brummelman; Krista den Ouden; Petra M de Bree; Monique A J van Eijndhoven; D Michiel Pegtel; Willem Stoorvogel; Thomas Würdinger; Marianne C Verhaar Journal: Blood Date: 2013-03-26 Impact factor: 22.113
Authors: William G Chang; Jillian W Andrejecsk; Martin S Kluger; W Mark Saltzman; Jordan S Pober Journal: Cardiovasc Res Date: 2013-09-16 Impact factor: 10.787
Authors: Paulina Kucharzewska; Helena C Christianson; Johanna E Welch; Katrin J Svensson; Erik Fredlund; Markus Ringnér; Matthias Mörgelin; Erika Bourseau-Guilmain; Johan Bengzon; Mattias Belting Journal: Proc Natl Acad Sci U S A Date: 2013-04-15 Impact factor: 11.205
Authors: Jillian W Andrejecsk; Jiajia Cui; William G Chang; Julie Devalliere; Jordan S Pober; W Mark Saltzman Journal: Biomaterials Date: 2013-08-21 Impact factor: 12.479
Authors: Carlos Salomon; Jennifer Ryan; Luis Sobrevia; Miharu Kobayashi; Keith Ashman; Murray Mitchell; Gregory E Rice Journal: PLoS One Date: 2013-07-08 Impact factor: 3.240
Authors: Ana E Paiva; Luiza Lousado; Daniel A P Guerra; Patrick O Azevedo; Isadora F G Sena; Julia P Andreotti; Gabryella S P Santos; Ricardo Gonçalves; Akiva Mintz; Alexander Birbrair Journal: Cancer Res Date: 2018-05-22 Impact factor: 12.701
Authors: Marie Billaud; Vera S Donnenberg; Bradley W Ellis; E Michael Meyer; Albert D Donnenberg; Jennifer C Hill; Tara D Richards; Thomas G Gleason; Julie A Phillippi Journal: Stem Cell Reports Date: 2017-05-25 Impact factor: 7.765
Authors: Markus Brown; Louise A Johnson; Dario A Leone; Peter Majek; Kari Vaahtomeri; Daniel Senfter; Nora Bukosza; Helga Schachner; Gabriele Asfour; Brigitte Langer; Robert Hauschild; Katja Parapatics; Young-Kwon Hong; Keiryn L Bennett; Renate Kain; Michael Detmar; Michael Sixt; David G Jackson; Dontscho Kerjaschki Journal: J Cell Biol Date: 2018-04-12 Impact factor: 10.539