Led by Leigh G. Griffiths, Ph.D., MRCVS, the Cardiovascular Tissue Engineering Research Laboratory at Mayo Clinic focuses on defining and overcoming barriers to human-to-human (allogeneic) and animal-to-human (xenogeneic) transplantation in people with cardiovascular disease.
Approaches to tissue engineering
All tissues and organs are composed of the same basic structures, consisting of cells, the supporting substance between cells (extracellular matrix) and signaling molecules.
The Cardiovascular Tissue Engineering Research Lab is working to combine these essential components to generate functional replacement tissues and organs. Several tissue engineering approaches are under intense investigation.
However, the key to achieving the seemingly simple goal of replicating normal tissue and organ development and growth remains elusive.
Dr. Griffiths' lab team has developed novel technologies for high-throughput immunoproteomic identification of HLA, non-HLA and nonprotein (for example, carbohydrate) antigens responsible for recipient graft-specific immune responses.
This work furthers the basic understanding of the molecular modulators of transplant rejection by:
- Facilitating development of biomarker panels to guide individualized medicine in transplant recipients
- Informing the design criteria for development of immunologically acceptable xenogeneic extracellular matrix scaffolds for cardiovascular regenerative medicine and tissue engineering applications
Host immune response challenges
The lab's regenerative medicine and tissue engineering work focuses on an animal-derived extracellular matrix (ECM) as a scaffold into which patient cells and signaling molecules can be placed to form the desired tissue or organ. Animal tissue is widely available and provides an ECM that is identical to that of the desired tissue type.
However, the critical impediment to use of an animal-derived ECM is that such material contains molecules that stimulate an aggressive host immune response (antigens) when implanted.
With these challenges in mind, Dr. Griffiths' lab has four main research objectives:
- Identify and understand the antigenic components of allogeneic and xenogeneic tissues and organs that stimulate an immune rejection response upon implantation
- Use principles of protein biochemistry to achieve removal of these antigenic components while leaving the ECM unchanged
- Investigate the interaction between cells and ECM scaffolds to achieve the goal of generating tissue-engineered tissues and organs
- Form immunologically acceptable ECM scaffold-based tissues and organs for clinical application
The Cardiovascular Tissue Engineering Research Lab has pioneered a new paradigm in the production of immunologically acceptable animal-derived ECM scaffolds, with preserved ECM structure-function relationships and recellularization capacity.
Through application of the lab's antigen-removal paradigm, the research team aims to overcome the previous obstacles to use xenogeneic scaffolds in tissue engineering applications.
Research work performed by Dr. Griffiths' lab team could ultimately help lead to better treatments for cardiovascular disease.