GMP-compatible Methods for producing tissue-engineered human heart muscle from stem cells
Heart tissue engineering using stem cells is a recently developed technique to construct a three dimensional cell/tissue structure from progenitor cells. Those engineered tissues can be either used for in vitro screenings (e.g. drug or toxicology screenings) or as a therapeutic tool to replace damaged or diseased tissue (regenerative medicine). Scientists at the University of Göttingen developed two new and fully defined methods for serum-free production of human engineered heart muscles (EHM) either from pre-differentiated cardiomyocytes or directly from undifferentiated stem cells. This will uniquely allow cardiological screening by measurement of muscular contraction (inotropic effects) on human tissue for the first time.
A major challenge in tissue engineering is the need for clearly defined compounds during cell/tissue differentiation. Furthermore, laboratory-grown tissue should resemble the natural organ’s tissue as closely as possible especially with respect to its physiologic function. This is essential for qualifying as a versatile tool in preclinical drug development.
Source: M. Tiburcy
Scientists at University of Göttingen, Medical Department developed two new and fully defined methods for serum-free production of human engineered heart muscles (EHM) either from pre-differentiated cardiomyocytes or directly from undifferentiated stem cells. This will allow production of human EHM under strict GMP standards. Moreover, the technologies will open the doors for a new generation of cardiological screening plattforms by measurement of muscular contraction (inotropic effects) on human tissue for the first time.
For cardiological screening (side effect or new compound screening):
For regenerative stem cell approach:
Serum-free production of force-generating human heart muscle (EHM). Source: M. Tiburcy.
Immunostaining of EHM showing well developed muscle bundles with anisotropically aligned cardiomyocytes. Source: M. Tiburcy.
The two GMP-compatible methods have been successfully established resulting in human engineered heart muscle tissue which resembles functionally native human heart muscle. Furthermore, cardiological screenings have been sucessfully performed and the screening platform is currently developed into an automated process.
We have filed patent applications in Europe and USA (Applicant: Georg-August-University of Göttingen public law foundation).
Dr. Stefan Uhle