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Advanced Cell Therapies for Cardiac Repair-SPUM

English title Advanced Cell Therapies for Cardiac Repair-SPUM
Applicant Hoerstrup Simon Philipp
Number 124090
Funding scheme SPUM
Research institution Klinik für Herz- und Gefässchirurgie Departement Chirurgie Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Cardiovascular Research
Start/End 01.04.2009 - 30.09.2013
Approved amount 2'998'421.00
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Keywords (18)

human mscs; microtissue technology; cardiac differentiation; cardiac stem cells; ischemic cardiac disease; cardiomyocyte; 3d hydrogel; animal model for myocardial infarction; huminized mice; inflammation; electrophysiology; Cell therapy, stem cells; heart failure; heart regeneration; mesenchymal stem cells; embryonic stem cells; induced pluripotent stem cells; cardiac progenitor cells, microtissues technology

Lay Summary (English)

Lead
Lay summary
Cell-based therapy raises tremendous hopes for the treatment of cardiac infarction and heart failure. Several cell types have shown promising results in animal studies. Driven by these expectations, a number of clinical trials have been initiated, mainly using bone marrow stem cells or skeletal myoblasts. However, the significant long-term improvement of cardiac function has not been achieved yet. Though cell-therapy seems to be safe, the modest beneficial effect is of short term and independent of the cell type used. Here we are going to develop advanced cell therapy for cardiac repair by joining forces of three leading institutions in Switzerland. The primary goal of the project is to achieve significant improvement of heart function using clinically relevant cell-based protocols and tissue engineering strategies. The expertise of the consortium ranges from human embryonic (hESC) and induced pluripotent stem cells (iPSC) to resident cardiac (CSC) and adult mesenchymal stem cells (MSC). The main objective of the project is to compare in a systematic manner the cell types at hands, and to evaluate whether it is possible to overcome cell-specific limitations. We will assess the best cell type (i), delivery format (ii) and delivery time (iii) in a defined sequence from in vitro to in vivo tests with regard to a realistic clinical implementation. The project will start by developing clinically relevant protocols for isolation, expansion and storage of human stem cells relevant for cardiac repair: MSC, CSC, iPSC and hESC. In a second phase, their cardiac differentiation capacity will be compared in vitro using conventional 2D culture as well as a 3D tissue culture system, i.e. microtissues. The best cell type for the cell therapy will be further evaluated in a small animal model. To address the best delivery method two novel application formats will be compared to the clinically established single cell suspensions. The evaluation criteria include the improvement of heart function, the structural and functional integration of the implanted cells and their tumorigenic potential. The two most promising cell type/application format combinations will be first validated in humanised mice. Thereafter, the optimal implantation time will be corroborated in preclinical large animal trials. Next to the development of novel cell therapy concept, the consortium provides the thoughtful training program for the clinical candidates. Their career development plans will enable them to qualify among the first generation of scientifically trained clinical specialists for the routine use of cell-based therapies for the treatment of cardiac diseases.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
150837 MicroSPECT/PET/CT for preclinical molecular imaging 01.12.2013 R'EQUIP

Abstract

Cell-based therapy raises big hopes for treatment of cardiac infarction and heart failure. Several cell types have shown promising therapeutic results in animal studies. Driven by these expectations, a number of clinical trials have been initiated, mainly using bone marrow stem cells or skeletal myoblasts. However, the significant long-term improvement of cardiac function has not yet been achieved. Though cell-therapy seems to be safe, the modest beneficial effect is of short term and independent of the cell type used. Only systematic investigation of clinically relevant human stem cell sources elucidating the cellular mechanisms of regeneration will allow for efficient clinical translation of cell-based therapies for cardiac repair.Here we are going to develop advanced cell therapy for cardiac repair by joining forces of three leading institutions in Switzerland, with respect to stem cells, cell therapy and tissue engineering. The primary goal of the project is to achieve the significant improvement of heart function using clinically relevant protocols for cell application. The unique expertise of the consortium comprises the range from human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) to more committed resident cardiac (CSCs) and adult mesenchymal stem cells (MSCs). Considering the complexity to screen for the “golden candidate”, we are going to assess the best cell type (i), delivery format (ii) and delivery time (iii) in a defined sequence from in vitro to in vivo tests with regard to realistic clinical implementation. To our knowledge, the direct comparison of such a comprehensive combination of different cells, application formats and time has not yet been performed in any other study.The project will start by developing clinically relevant protocols for isolation, expansion and storage of human stem cells relevant for cardiac repair: MSCs, CSCs, iPSCs and hESCs (WP1). In a second phase, their cardiac differentiation capacity will be directly compared in vitro using conventional 2D culture as well as in a 3D tissue culture model system, microtissues (WP2). The best cell type for the cell therapy will be further evaluated in a small animal model. To address the best delivery method two novel application formats, microtissues and gel based cell suspensions will be compared to the clinically established single cell suspensions. The evaluation criteria include improvement of heart function, structural and functional integration of the implanted cells and their tumorigenic potential. The two most promising cell types/application format combinations will be further validated in humanised mice for their inflammatory induction (WP3). Further, the optimal implantation time will be specified in preclinical large animal trails (WP4). Next to the development of a novel cell therapy concept, the consortium provides the thoughtful training program for the clinical candidates. Their career development plans will enable them to acquire a large experience in cardiovascular regenerative therapies and to qualify among the first generation of scientifically trained clinical specialists for the routine use of cell-based therapies for the treatment of cardiac diseases. During the last year of the project the candidates will prepare and translate the clinical trials in collaboration with the Clinical Trial Centre (CTC) and the authorities (WP5).The expertise built through the interdisciplinary network of the SPUM consortium will substantially benefit translational clinical research and bring Switzerland at the forefront in the development of advanced cell-based therapies.
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