archives@tulane.edu / Osteoarthritis (OA) is a common joint disorder with significant economic and healthcare impact. The knee joint is composed of cartilage and the adjoining bone, a synovial capsule, the infrapatellar fat pad (IPFP), and other connective tissues such as tendons and ligaments. Adipose tissue has recently been highlighted as a major contributor to OA through strong inflammation mediating effects. Type II diabetes mellitus (T2D) is a weight independent risk factor for OA, suggesting a link between OA and adipose dysfunction that has yet to be elucidated. There is a critical need for development of new methodologies to investigate the interaction between an osteochondral interface and extra-synovial tissue. There is also a need for investigating adipose derived stem cells (ASCs) isolated from the IPFP of T2D patients as a potential cell source to model diabetic complications.
In this work, we develop a novel 3D printed bioreactor model for incorporation into a previously established osteoarthritic knee microphysiological system. Using our established model, we investigated xenoprotein free (XPF) media as a potential commercial product for the MPS industry. Additionally, differences in inflammatory and adipokine related mRNA expression of IPFP-ASCs isolated from non-diabetic (Non-T2D), pre-diabetic (Pre-T2D), and type II diabetes mellitus (T2D) patient samples were analyzed.
After 28 Days of differentiation, 3D printer bioreactors using commercially available AdipoQual media exhibited robust increase in adipokine expression and neutral lipid accumulation. Bioreactors cultured with a novel XPF supplemented
AdipoQual had similar adipokine expression but no neutral lipid accumulation. Pre-T2D IPFP-ASCs exhibited a robust decrease in CD90 and CD105 levels with no corresponding increase in markers for potentially contaminating cell types. Cox-2 expression and PGE2 secretion were significantly increased in IL-1β stimulated Pre-T2D IPFP-ASCs compared to Non-T2D and T2D IPFP-ASCs. When the Pre-T2D ASCs were co-cultured with M1-induced macrophages, the macrophages significantly reduced expressions of tumor necrosis factor α (TNFα) and IL-6 compared to M1-induced macrophages co-cultured with Non-T2D and T2D IPFP-ASCs. Taken together, this work has taken significant steps towards establishment of a model for the IPFP and establishment of important phenotypic and genotypic changes of IPFP-ASCs isolated from Pre-T2D patients. / 1 / Benjamen O'Donnell
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_121701 |
| Date | January 2020 |
| Contributors | O'Donnell, Benjamen (author), Bunnell, Bruce (Thesis advisor), School of Science & Engineering Interdisciplinary Bioinnovation PhD Program (Degree granting institution), NULL (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 149 |
| Rights | 6 months, Copyright is in accordance with U.S. Copyright law. |
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