With the recruitment of Jörg Gerlach to the McGowan Institute for Regenerative Medicine, the Institute has established an interdisciplinary research group working on methods for the clinical translation of tissue engineering for stem cell biology by providing biotechnology tools for stem cell-based therapy.
The group’s research focuses building 3D perfusion culture bioreactors that combine synthetic components with human cells or stem cells to scale-up cell availability and create support and cell transplantation therapies.
The McGowan Institute for Regenerative Medicine serves as a single base of operations for the University of Pittsburgh’s leading engineers, cell biologists, and clinical faculty working to advance the science of regenerative medicine, cellular therapies, and artificial and biohybrid organ devices, and to effectively translate these innovative technologies into clinical practices where patients can benefit.
The group is working with cells from the liver, skin, bone marrow, neuronal cells and stem cells (adult, fetal, embryonic). The clinical focus is on the development of systems for temporary support from outside the body and on growing human liver cells in bioreactors for progenitor cell transplantation.
We take a systems approach, to bridge basic sciences with technological and clinical disciplines. Our result-oriented developments bring together technological “know-how” and clinical “know-why”, and will be measured on clinical success.
We work together with several engineering and cell biology groups at the University of Pittsburgh and outside of our facility and conduct a close collaboration with groups in Europe, including the Division of Experimental Surgery, Charité Medical Faculty of the Humboldt University Berlin, Germany. International networking activities are managed through our CellNet.org initiative.
Summary of Activities
The Bioreactor Group Team mission statement focuses on bioengineering technologies for in vitro 3D tissue regeneration and stem cell culture. The research interests include in vitro maintenance and differentiation of cells for extracorporeal, temporary clinical use as a hybrid organ, production of cells in bioreactors for cell-based therapy, and production of regenerative mediators by cells for applications in Regenerative Medicine.
The goals of our labs are to understand the control of cell differentiation, cell maintenance in vitro proliferation at the cellular level, and to study the role of physiological aspects. These include cell density and perfusion, macroenvironmental gradients, oxygen tension, the culture of parenchymal and non-parenchymal cells. Studies with collaborators aim to understand such mechanisms at the molecular level.
We study the differentiation of stem cells using several model systems.
Applying the technology platforms, we develop bioreactor technologies for the provision of cells for Regenerative Medicine and blood perfusion systems for extracorporeal organ assist. This is performed in collaboration with the University of Berlin and an international network of researchers.
The labs develop primary- and stem cell in vitro culture models. In addition to liver cells, we work also on skin-, bone marrow-, neuronal cells and embryonic stem cell lines.
Liver Cell Systems
Our knowledge of cellular pathways and bioengineering tools has allowed us to use fetal and adult liver progenitor cells to produce functional liver tissue in vitro. Our work suggests that critical factors for liver stem cell development are also needed to maintain essential functions of the mature liver cells.
Using such model systems we study the role of multi-compartment high-density perfusion culture on 3D in vitro cell restructuring. We have shown that co-culturing parenchymal and non-paranechymal liver cells in four compartment 3D perfusion systems can achieve a neo formation of liver sinusoidal structures and space-of- Disse like structures. A re-structuring of the canal of Hering enabled us to proliferate liver progenitor cells in vitro.
In the process of clinical translation of tissue developments into cell-based therapies in transplantation medicine and intensive care, we study the role of extracorporeal liver cell perfusion in human liver disease and investigate how temporary liver support may help in acute & acute-on chronic liver failure, and bridging to liver transplantation or during initial transplant dysfunction.
Podcast: December 2013
Podcast: June 2008
McGowan Institute for Regenerative Medicine
3025 East Carson Street
Pittsburgh, PA 15203
Jim Harris, Research Coordinator 412-383-7460