title: Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.
abstract: Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.
authors.affiliation: 1] Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Singapore, Singapore [2] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [3] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore [4] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Blocki
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore [3] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.
authors.forename: Yingting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore.
authors.forename: Maria
authors.initials: M
authors.lastname: Koch
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Goralczyk
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore [3] Singapore MIT Alliance for Research and Technology (SMART), Singapore, Singapore.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beyer
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Singapore, Singapore.
authors.forename: Nikita
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore [3] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Singapore, Singapore.
authors.forename: Shehzahdi
authors.initials: S
authors.lastname: Moonshi
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore [3] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Dewavrin
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Peh
authors.affiliation: 1] NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore [2] Department of Physiology, National University of Singapore, Singapore, Singapore.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
authors.affiliation: 1] Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Singapore, Singapore [2] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Kishore
authors.initials: K
authors.lastname: Bhakoo
authors.affiliation: 1] Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore [2] NUS Tissue Engineering Programme, (Life Sciences Institute), National University of Singapore, Singapore, Singapore [3] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Raghunath
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D015870:Gene Expression; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D061251:Primary Cell Culture; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D015415:Biomarkers; D011509:Proteoglycans; D020797:Receptor, Platelet-Derived Growth Factor beta; D000099216:Chondroitin Sulfate Proteoglycan 4