title: Potency of Human Cardiosphere-Derived Cells from Patients with Ischemic Heart Disease Is Associated with Robust Vascular Supportive Ability.
abstract: Cardiosphere-derived cell (CDC) infusion into damaged myocardium has shown some reparative effect; this could be improved by better selection of patients and cell subtype. CDCs isolated from patients with ischemic heart disease are able to support vessel formation in vitro but this ability varies between patients. The primary aim of our study was to investigate whether the vascular supportive function of CDCs impacts on their therapeutic potential, with the goal of improving patient stratification. A subgroup of patients produced CDCs which did not efficiently support vessel formation (poor supporter CDCs), had reduced levels of proliferation and increased senescence, despite them being isolated in the same manner and having a similar immunophenotype to CDCs able to support vessel formation. In a rodent model of myocardial infarction, poor supporter CDCs had a limited reparative effect when compared to CDCs which had efficiently supported vessel formation in vitro. This work suggests that not all patients provide cells which are suitable for cell therapy. Assessing the vascular supportive function of cells could be used to stratify which patients will truly benefit from cell therapy and those who would be better suited to an allogeneic transplant or regenerative preconditioning of their cells in a precision medicine fashion. This could reduce costs, culture times and improve clinical outcomes and patient prognosis. Stem Cells Translational Medicine 2017;6:1399-1411.
authors.affiliation: Radcliffe Department of Medicine.
authors.forename: Emma
authors.initials: E
authors.lastname: Harvey
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.|R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, United Kingdom.
authors.forename: Huajun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepúlveda
authors.affiliation: Department of Haematology.|British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge, United Kingdom.|R&D Division, National Health Service (NHS)-Blood and Transplant, Cambridge Centre, Cambridge, United Kingdom.
authors.forename: Sara P
authors.initials: SP
authors.lastname: Garcia
authors.affiliation: Radcliffe Department of Medicine.|R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, United Kingdom.
authors.forename: Dominic
authors.initials: D
authors.lastname: Sweeney
authors.affiliation: Department of Haematology.|British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Fizzah A
authors.initials: FA
authors.lastname: Choudry
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.|R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, United Kingdom.
authors.forename: George N
authors.initials: GN
authors.lastname: Thomas
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Hassan
authors.initials: H
authors.lastname: Kattach
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.|Department of Haematology.
authors.forename: Romina
authors.initials: R
authors.lastname: Petersen
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Blake
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: David P
authors.initials: DP
authors.lastname: Taggart
authors.affiliation: Department of Haematology.|British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge, United Kingdom.|R&D Division, National Health Service (NHS)-Blood and Transplant, Cambridge Centre, Cambridge, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Frontini
authors.affiliation: Radcliffe Department of Medicine.|R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, United Kingdom.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Watt
authors.affiliation: Radcliffe Department of Medicine.|R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, United Kingdom.
authors.forename: Enca
authors.initials: E
authors.lastname: Martin-Rendon
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D003324:Coronary Artery Disease / Q000628:therapy*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017202:Myocardial Ischemia / Q000628:therapy*; D013234:Stem Cells / Q000166:cytology*
keywords: Cell-based and tissue-based therapy; Coronary artery disease; Humans; Myocardial ischemia; Tissue-specific progenitor cells