Potency of Human Cardiosphere-Derived Cells from Patients with Ischemic Heart Disease Is Associated with Robust Vascular Supportive Ability

Author:

Harvey Emma1,Zhang Huajun23,Sepúlveda Pilar4,Garcia Sara P.567,Sweeney Dominic13,Choudry Fizzah A.57,Castellano Delia4,Thomas George N.23,Kattach Hassan2,Petersen Romina45,Blake Derek J.8,Taggart David P.2,Frontini Mattia567,Watt Suzanne M.13,Martin-Rendon Enca13

Affiliation:

1. a Radcliffe Department of Medicine, Oxford, United Kingdom

2. b Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom

3. c R&D Division, National Health Service (NHS)-Blood and Transplant, Oxford Centre, Oxford, United Kingdom

4. d Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain

5. e Department of Haematology, Cambridge, United Kingdom

6. g R&D Division, National Health Service (NHS)-Blood and Transplant, Cambridge Centre, Cambridge, United Kingdom

7. f British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge, United Kingdom

8. h MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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