The Gruh research group is focusing on the establishment and characterization of bioartificial cardiac tissue (BCT) for therapeutic application and disease modelling.
Key aspects of our research, i.e. stem cell research and tissue engineering have a very interdisciplinary character, including aspects of biology, chemistry and physics, as well as (pre-)clinical application. In frame of different research projects we are collaborating with other groups at LEBAO and other departments at Hannover Medical School and Leibniz University Hannover as well as international partners.
The group was established as a junior research group for ‘Myocardial Tissue Engineering’ within the cluster of excellence REBIRTH, and receives ongoing support from the 'REBIRTH - Research Center for Translational Regenerative Medicine'.
Heart muscle tissue for therapeutic application
For a number of cardiovascular diseases transplantation of bioartificial cardiac tissue generated from stem cells could be an alternative to organ transplantation. It could be used to replace injured tissue after myocardial infarction or to reconstruct congenital malformations of the heart.
In the Gruh lab, we established methods for the generation of bioartificial cardiac tissue (BCTs) with neonatal rat cardiomyocytes. Together with Leibniz University Hannover, we tested matrices for tissue engineering, including methacrylated alginate and hyaluronic acid blends and novel in situ cross-linking polymers – all with the common goal to develop non-immunogenic materials for clinical application. These technologies were then combined for the generation of murine and human heart muscle tissue from embryonic and induced pluripotent stem cells.
For clininical testing of bioartificial cardiac tissue, we currently aim at standardizing procedures and establishing validation assays. The Gruh lab is involved in studies on therapeutic cell transplantation in frame of the BMBF-funded project iCARE - Induced pluripotent stem cells for clinically applicable heart repair – with six partner institutions, coordinated by Prof. Dr. U. Martin and Prof. Dr. A. Haverich (LEBAO, HTTG, MHH).
The BMBF-funded project 3D-Heart-2B coordinated by Prof. Dr. Ina Gruh aims at the generation of a tube-shaped heart tissue, which is based on the contractile function of human pluripotent stem cell-derived cardiomyocytes. The tubular construct represents a single heart chamber and is supposed to allow for directional pumping with sufficient efficiency to support impaired heart function.
In vitro disease modelling
Another part of our research focuses on the implementation of bioartificial cardiac tissue as in vitro model of cardiac physiology and pathophysiology. In previous projects, we have investigated pharmacological influences on tissue functionality and used bioartificial cardiac tissue as in vitro models to study hypertrophy and fibrosis. Currently, we have extended this model using patient-specific iPSCs for disease modeling to investigate genetic causes of cardiovascular diseases and develop novel treatment strategies.
Novel technologies: bioreactors, biomaterials, biohybrids
We have investigated tissue functionality in different bioreactor systems, which are modified and developed further in ongoing projects. Addressing the problem that limited numbers of stem cell-derived cardiomyocytes had been available previously, we developed a multimodal bioreactor for cultivation and functional testing of miniaturized bioartificial cardiac tissue. These small-scale tissues are especially suitable for in vitro disease modelling. For therapeutic application, larger tissues and modified bioreactors are needed. Therefore, in ongoing project we are optimizing tissue composition (cell types and matrix components) and vascularization for large-scale tissue of clinically relevant dimensions.
The BMBF-funded project BioPACE (Biohybrids for photon-activated cardiac excitation) headed by Prof. Dr. Alexander Heisterkamp (LZH/NIFE) aims at combining stem cell-based engineered tissue with photonics, optogenetics and nanotechnology to establish a new strategy for the treatment of cardiovascular disease, which could potentially offer an alternative to conventional electric pacemaker devices.
Read more here: BIOPACE