The research efforts of
McGowan Institute for Regenerative Medicine
faculty member Kacey Marra, PhD, associate professor, Department of Surgery, and co-director of the Adipose Stem Cell Center, University of Pittsburgh, and her colleagues McGowan Institute for Regenerative Medicine faculty members Jörg Gerlach, MD, PhD, professor, Department of Surgery, University of Pittsburgh, and J. Peter Rubin, MD, chief of the UPMC Division of Plastic and Reconstructive Surgery and director of the UPMC Center for Innovation in Restorative Medicine, and co-director of the Adipose Stem Cell Center, were not only published in Tissue Engineering Part C: Methods, but were featured on the journal’s cover. Their paper is entitled “Adipogenesis of Human Adipose-Derived Stem Cells Within Three-Dimensional Hollow Fiber-Based Bioreactors” and presents the development of a coherent 3D high density fat-like tissue consisting of unilocular structure from primary adipose stem cells in vitro.
The abstract of the prominent article reads:
To further differentiate adipose-derived stem cells (ASCs) into mature adipocytes and create three-dimensional (3D) adipose tissue in vitro, we applied multicompartment hollow fiber-based bioreactor technology with decentral mass exchange for more physiological substrate gradients and integral oxygenation. We hypothesize that a dynamic 3D perfusion in such a bioreactor will result in longer-term culture of human adipocytes in vitro, thus providing metabolically active tissue serving as a diagnostic model for screening drugs to treat diabetes. ASCs were isolated from discarded human abdominal subcutaneous adipose tissue and then inoculated into dynamic 3D culture bioreactors to undergo adipogenic differentiation. Insulin-stimulated glucose uptake from the medium was assessed with and without TNF-alpha. 3D adipose tissue was generated in the 3D-bioreactors. Immunohistochemical staining indicated that 3D-bioreactor culture displayed multiple mature adipocyte markers with more unilocular morphologies as compared with two-dimensional (2D) cultures. Results of real-time polymerase chain reaction showed 3D-bioreactor treatment had more efficient differentiation in fatty acid-binding protein 4 expression. Repeated insulin stimulation resulted in increased glucose uptake, with a return to baseline between testing. Importantly, TNF-alpha inhibited glucose uptake, an indication of the metabolic activity of the tissue. 3D bioreactors allow more mature adipocyte differentiation of ASCs compared with traditional 2D culture and generate adipose tissue in vitro for up to 2 months. Reproducible metabolic activity of the adipose tissue in the bioreactor was demonstrated, which is potentially useful for drug discovery. We present here, to the best of our knowledge for the first time, the development of a coherent 3D high density fat-like tissue consisting of unilocular structure from primary adipose stem cells in vitro.
Illustration: Tissue Engineering Part C: Methods.
Bio: Dr. Jörg Gerlach
Bio: Dr. J. Peter Rubin
Bio: Dr. Kacey Marra
Abstract (Adipogenesis of Human Adipose-Derived Stem Cells Within Three-Dimensional Hollow Fiber-Based Bioreactors. Jörg C. Gerlach, Yen-Chih Lin, Candace A. Brayfield, Danielle M. Minteer, Han Li, J. Peter Rubin, and Kacey G. Marra. Tissue Engineering Part C: Methods. January 2012, 18(1): 54-61.)