TY - JOUR
T1 - 476 Discovery and Characterisation of Bipotent, Angiogenic Haemangioblast Progenitor Cells in Adult Human Vasculature
AU - Long, A.
AU - Williamson, A.
AU - Liyanage, S.
AU - Salagaras, T.
AU - Dimasi, C.
AU - Fernando, S.
AU - Primer, K.
AU - Hassanshahi, M.
AU - Tan, J.
AU - Fitridge, R.
AU - Worthington, M.
AU - Bursill, C.
AU - Psaltis, P.
PY - 2020/11
Y1 - 2020/11
N2 - Background: The vascular adventitia contains progenitor cells and vasa vasorum, which play an important role in atherosclerosis. We previously discovered the presence of Lin-CD45+Sca-1+ colony forming unit-macrophage (CFU-M) progenitor cells in murine arterial adventitia. These progenitors have bipotent differentiation capacity for endothelial cells and macrophages, contributing to vasa vasorum expansion. Here we investigated for the existence of analogous progenitor cells in human vasculature. Methods & Results: We first confirmed the presence of CFU-M progenitors in human vessels by culturing single cell digests from saphenous vein (SV) and left internal mammary artery (LIMA) in Methylcellulose for 14d. SV CFU-M yield was >50% greater than LIMA (p=0.0002). Fluoresce activated cell sorting of SV digests identified that CFU-M arise from a unique CD45+CD31-cKit+CD34+ subpopulation. Progenitor cells isolated from cultured CFU-M were plated in Matrigel and displayed angiogenic capacity by forming branching cords after 7d, containing endothelial cells and macrophages, indicating bipotent differentiation. As diabetes was associated with reduced recovery of CFU-M from human SV, we used streptozotocin-induced diabetic mice to study the effect of hyperglycaemia. Aortic CFU-M progenitors from diabetic mice displayed reduced clonogenic (p=0.006), self-renewal (p=0.028) and angiogenic capacity (p=0.048) compared to non-diabetic controls. Similar inhibitory effects were induced by exposing CFU-M progenitors from healthy mouse aorta to high glucose concentration in culture. Finally, hyperglycaemia and glucose conditioning also resulted in metabolic changes to CFU-M progenitors, including reduced mitochondrial respiration. Conclusion: Human vasculature contains CD45+CD31-cKit+CD34+ CFU-M progenitors which possess angiogenic capacity and haemangioblast-like, bipotent differentiation potential. Hyperglycaemia and increased glucose exposure inhibit the stem-like properties of these cells.
AB - Background: The vascular adventitia contains progenitor cells and vasa vasorum, which play an important role in atherosclerosis. We previously discovered the presence of Lin-CD45+Sca-1+ colony forming unit-macrophage (CFU-M) progenitor cells in murine arterial adventitia. These progenitors have bipotent differentiation capacity for endothelial cells and macrophages, contributing to vasa vasorum expansion. Here we investigated for the existence of analogous progenitor cells in human vasculature. Methods & Results: We first confirmed the presence of CFU-M progenitors in human vessels by culturing single cell digests from saphenous vein (SV) and left internal mammary artery (LIMA) in Methylcellulose for 14d. SV CFU-M yield was >50% greater than LIMA (p=0.0002). Fluoresce activated cell sorting of SV digests identified that CFU-M arise from a unique CD45+CD31-cKit+CD34+ subpopulation. Progenitor cells isolated from cultured CFU-M were plated in Matrigel and displayed angiogenic capacity by forming branching cords after 7d, containing endothelial cells and macrophages, indicating bipotent differentiation. As diabetes was associated with reduced recovery of CFU-M from human SV, we used streptozotocin-induced diabetic mice to study the effect of hyperglycaemia. Aortic CFU-M progenitors from diabetic mice displayed reduced clonogenic (p=0.006), self-renewal (p=0.028) and angiogenic capacity (p=0.048) compared to non-diabetic controls. Similar inhibitory effects were induced by exposing CFU-M progenitors from healthy mouse aorta to high glucose concentration in culture. Finally, hyperglycaemia and glucose conditioning also resulted in metabolic changes to CFU-M progenitors, including reduced mitochondrial respiration. Conclusion: Human vasculature contains CD45+CD31-cKit+CD34+ CFU-M progenitors which possess angiogenic capacity and haemangioblast-like, bipotent differentiation potential. Hyperglycaemia and increased glucose exposure inhibit the stem-like properties of these cells.
UR - https://www.mendeley.com/catalogue/72107b3f-dbef-3401-a83c-a9b7dfe1cf33/
U2 - 10.1016/j.hlc.2020.09.483
DO - 10.1016/j.hlc.2020.09.483
M3 - Article
VL - 29
SP - S251
JO - Heart, Lung and Circulation
JF - Heart, Lung and Circulation
ER -