Stem Cell based 3D Microtisssue Technology Platform for cardiac regeneration
Stem cells have been suggested as a next generation therapeutic approach for the treatment of heart failure due to myocardial infarction or cardiomyopathy. Based on pre-clinical animal trials, there are increasing numbers of early phase patient studies aiming to demonstrate the feasibility and potential efficacy of stem cell-based therapies in the clinical setting. However, although stem cells have shown great potential and created substantial clinical hope, the anticipated beneficial effects (improvement of cardiac function) so far have been marginal. One major reason is the too rapid translation from small animal studies or non-comparable large animal studies into human studies, while key questions with regards to the so called "stem cell fate", have not been elucidated yet.
Fig. 1 Mesenchymal stem cell based 3D microtissues
The aim of this research is the development of translational, clinically relevant stem cell based 3D bio-engineering concepts for cardiac regeneration. We focus on the assessment of clinically relevant stem cell sources and the evaluation of advanced, 3Dstem cell delivery formats. Based on the hanging drop method, the novel 3D microtissue technology allowing for a 3D cellular self-assembly was developed at the Swiss Center for Regenerative Medicine and is being tested in animal disease models for cardiac regeneration. A further objective is to translate the concept of 3D microtissues in a Good Laboratory Practice compliant manner preclinical setting (porcine myocardial infarction model) as an important step before entering the clinical setting. We esthablished a state-of-the-art electromechanical mapping guided transcatheter NOGA technology. That will allow for the most accurate definition of the border zone of myocardial infarction (via endocardial electromechanical mapping of the ventricle) and to deliver the 3D microtissues.
Fig. 2 Intramyocardial injection of human mesenchymal stem cell based 3D microtissues using the NOGA transcatheter based three dimensional mapping (left). Histological assessment of 3D-MTs post transplantation (right). (Emmert et al. Biomaterials 2013.)