There is the hypothesis that many patients burdened with a variety of organ insufficiencies might be better served by optimizing the regenerative potential. Based on this hypothesis engineering and biologic principles are applied to assess disease processes and to implement tissue regenerative technologies to augment the patients own organ healing process in the body. Based on the mentioned hypothesis, research is directed to assess and model disease processes, to develop extracorporeal organ support technologies, and to assess how best to implement organ support technologies to augment the patients own organ healing process.
The term "regenerative medicine" was introduced to describe this promising new area of biomedical development. Examples of such research areas include:
- Pharmaceutical intervention (e.g. local growth factor delivery) by mediators produced by cell culture systems
- Cell-based therapies (e.g. local stem cell injections) with reparative cells produced by bioreactors, and
- Functional unloading to enable organ regeneration using extracorporeal temporary organ support provided by active cells in bioreactors (e.g. in acute liver failure).
Bioreactors provide technology platforms for the production of regenerative mediators by working cells. They also enable cell multiplication to provide transplantable reparative cells, and they are being developed for extracorporeal organ support using cell cultures. 3-D technologies support tissue formation at a high cell density in vitro. Medium perfusion systems and integrated oxygenation allow cell maintenance, differentiation or growth in vitro. Specific cells of the tissues are co-cultured to enable cellular communication and mediator exchange in the bioreactor. More advanced systems support culture and expansion/differentiation of adult stem cells.
The group initially address liver-, skin-, bone marrow-, and stem cells. However, our underlying premise is that an organ system must be functionally relieved or "unloaded" to facilitate the inherent healing process, or to allow an augmentation of organ healing. In the case of a cardiac assist device this unloading may be purely mechanical in nature, whereas in a liver assist device the unloading may have multiple chemical determinants. How this functional unloading is best achieved and implemented depends on the extent of our understanding of the underlying disease process and our ability to design and develop appropriate technologies to assume part or all of the functional burden. In the field of liver cells, we focus on acute liver support systems using an extracorporeal assist system.
For each of the organ systems we are investigating, an array of functionally assistive technologies that have already been developed and clinically evaluated, ranging from widely used devices in kidney failure, to experimental devices achieving limited success in the area of liver support. For each system the assistive technology replaces specific functions of the failing organ in a defined temporal manner. It is often unclear, however, whether or not the relevant functions are addressed, whether the functions assumed are adequate and of a sufficient magnitude, and whether or not an appropriate time course is followed to best facilitate recovery of the failing organ system. Designs to be worked on in the group range from the purely synthetic and mechanical (e.g. charcoal/resin adsorption and dialysis) to bio-hybrid organs where some biological component is incorporated (e.g. the function of the human liver cell populations).
In a diseased or traumatized state, an organ system may directly or indirectly provide positive feedback for the failure process. By removing the functional load for that organ system and the connected physiological systems, the intrinsic healing process may be facilitated (e.g. myocardial recovery following ventricular unloading with mechanical circulatory support). This intrinsic healing may involve tissue remodeling by resident cells within the organ, the recruitment of the nearby or circulating stem cells to the damaged organ to regenerate functional tissue, or a variety of other healing mechanisms.
There are clearly many states of disease and trauma where organ recovery is not feasible and replacement (by organ transplantation or artificial organs) remains the only viable option. On the other hand, there are many states of organ failure where there appears to be a lack of intrinsic healing ability, but where interventional therapies may facilitate the healing process. Examples of such therapies, and the topics of our group include:
- Pharmaceutical intervention (e.g. local growth factor delivery) by mediators produced by cell culture systems, and
- Regenerative cell transplantation (e.g. local stem cell injections), requiring cell production by bioreactors.
This augmented organ healing would be similarly facilitated by the creation of a hospitable local environment for the organ regeneration by the functional unloading of organ function, requiring extracorporeal temporary organ support with bioreactors. The development of a modular extracorporeal liver support concept and a specific bioreactor construction as the cell module is actually the main topic of the group.
Additional information on the Gerlach Lab
CONTACT INFORMATION
Dr. Jörg GerlachPhone: 412-383-7150
Email: jgerlach@pitt.edu