@article{nordberg_huebner_schuchard_mellor_shirwaiker_loboa_spang_2021, title={The evaluation of a multiphasic 3D-bioplotted scaffold seeded with adipose derived stem cells to repair osteochondral defects in a porcine model}, volume={6}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.34886}, abstractNote={AbstractThere is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D‐bioplotted osteochondral scaffold design that can drive site‐specific tissue formation when seeded with adipose‐derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and compared to both open lesions and autologous explants. ICRS II evaluation indicated that defects with ASC‐seeded scaffolds had healing that most closely resembled the aulogous explant. Scaffold‐facilitated subchondral bone repair mimicked the structure of native bone tissue, but cartilage matrix staining was not apparent within the scaffold. The open lesions had the highest volumetric infill detected using CT analysis (p < 0.05), but the repair tissue was largely disorganized. The acellular scaffold without a tidemark had significantly more volumetric filling than either the acellular or ASC seeded groups containing a tidemark (p < 0.05), suggesting that the tidemark limited cell infiltration into the cartilage portion of the scaffold. Overall, scaffold groups repaired the defect more successfully than an open lesion but achieved limited repair in the cartilage region. With further optimization, this approach holds potential to treat focal cartilage lesions in a highly personalized manner using a human patient's own ASC cells.}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Nordberg, Rachel C. and Huebner, Pedro and Schuchard, Karl G. and Mellor, Liliana F. and Shirwaiker, Rohan A. and Loboa, Elizabeth G. and Spang, Jeffery T.}, year={2021}, month={Jun} } @article{mellor_nordberg_huebner_mohiti-asli_taylor_efird_oxford_spang_shirwaiker_loboa_2020, title={Investigation of multiphasic 3D-bioplotted scaffolds for site-specific chondrogenic and osteogenic differentiation of human adipose-derived stem cells for osteochondral tissue engineering applications}, volume={108}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.34542}, abstractNote={AbstractOsteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D‐bioplotting of biodegradable polycraprolactone (PCL) with either β‐tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site‐specific hASC osteogenesis and chondrogenesis, respectively. PCL‐dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D‐bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC‐seeded 3D‐bioplotted PCL‐TCP, electrospun PCL, and 3D‐bioplotted PCL‐dECM phases were evaluated and demonstrated site‐specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.}, number={5}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Mellor, Liliana F. and Nordberg, Rachel C. and Huebner, Pedro and Mohiti-Asli, Mahsa and Taylor, Michael A. and Efird, William and Oxford, Julia T. and Spang, Jeffrey T. and Shirwaiker, Rohan A. and Loboa, Elizabeth G.}, year={2020}, month={Jul}, pages={2017–2030} } @article{watson_nordberg_loboa_kullman_2019, title={Evidence for Aryl hydrocarbon Receptor-Mediated Inhibition of Osteoblast Differentiation in Human Mesenchymal Stem Cells}, volume={167}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfy225}, abstractNote={Multipotent mesenchymal stem cells (MSCs) maintain the ability to differentiate into adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing concern that exposure to environmental agents such as aryl hydrocarbon receptor (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone formation. The objective of the current study was to evaluate the potential of the prototypic AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to disrupt osteogenic differentiation of human bone-derived MSCs (hBMSCs) in vitro. Primary hBMSCs from three donors were exposed to 10 nM TCDD and differentiation was interrogated using select histological, biochemical, and transcriptional markers of osteogenesis. Exposure to 10 nM TCDD resulted in an overall consistent attenuation of alkaline phosphatase (ALP) activity and matrix mineralization at terminal stages of differentiation in primary hBMSCs. At the transcriptional level, the transcriptional regulator DLX5 and additional osteogenic markers (ALP, OPN, and IBSP) displayed attenuated expression; conversely, FGF9 and FGF18 were consistently upregulated in each donor. Expression of stem cell potency markers SOX2, NANOG, and SALL4 decreased in the osteogenic controls, whereas expression in TCDD-treated cells resembled that of undifferentiated cells. Coexposure with the AhR antagonist GNF351 blocked TCDD-mediated attenuation of matrix mineralization, and either fully or partially rescued expression of genes associated with osteogenic regulation, extracellular matrix, and/or maintenance of multipotency. Thus, experimental evidence from this study suggests that AhR transactivation likely attenuates osteoblast differentiation in multipotent hBMSCs. This study also underscores the use of primary human MSCs to evaluate osteoinductive or osteotoxic potential of chemical and pharmacologic agents in vitro.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Watson, AtLee T. D. and Nordberg, Rachel C. and Loboa, Elizabeth G. and Kullman, Seth W.}, year={2019}, month={Jan}, pages={145–156} } @article{mellor_steward_nordberg_taylor_loboa_2017, title={Comparison of simulated microgravity and hydrostatic pressure for chondrogenesis of hASC}, volume={88}, number={4}, journal={Aerospace Medicine and Human Performance}, author={Mellor, L. F. and Steward, A. J. and Nordberg, R. C. and Taylor, M. A. and Loboa, E. G.}, year={2017}, pages={377–384} } @article{nordberg_zhang_griffith_frank_starly_loboa_2017, title={Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation}, volume={6}, ISSN={["2157-6580"]}, DOI={10.5966/sctm.2015-0404}, abstractNote={Abstract Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applications. However, a critical issue to be addressed before widespread hASC clinical translation is the dramatic variability in proliferative capacity and osteogenic potential among hASCs isolated from different donors. The goal of this study was to test our hypothesis that electrical cell-substrate impedance spectroscopy (ECIS) could track complex bioimpedance patterns of hASCs throughout proliferation and osteogenic differentiation to better understand and predict variability among hASC populations. Superlots composed of hASCs from young (aged 24–36 years), middle-aged (aged 48–55 years), and elderly (aged 60–81 years) donors were seeded on gold electrode arrays. Complex impedance measurements were taken throughout proliferation and osteogenic differentiation. During osteogenic differentiation, four impedance phases were identified: increase, primary stabilization, drop phase, and secondary stabilization. Matrix deposition was first observed 48–96 hours after the impedance maximum, indicating, for the first time, that ECIS can identify morphological changes that correspond to late-stage osteogenic differentiation. The impedance maximum was observed at day 10.0 in young, day 6.1 in middle-aged, and day 1.3 in elderly hASCs, suggesting that hASCs from younger donors require a longer time to differentiate than do hASCs from older donors, but young hASCs proliferated more and accreted more calcium long-term. This is the first study to use ECIS to predict osteogenic potential of multiple hASC populations and to show that donor age may temporally control onset of osteogenesis. These findings could be critical for development of patient-specific bone tissue engineering and regenerative medicine therapies.}, number={2}, journal={STEM CELLS TRANSLATIONAL MEDICINE}, author={Nordberg, Rachel C. and Zhang, Jianlei and Griffith, Emily H. and Frank, Matthew W. and Starly, Binil and Loboa, Elizabeth G.}, year={2017}, month={Feb}, pages={502–511} } @article{nordberg_charoenpanich_vaughn_griffith_fisher_cole_spang_loboa_2016, title={Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method}, volume={11}, journal={Journal of Orthopaedic Surgery and Research}, author={Nordberg, R. C. and Charoenpanich, A. and Vaughn, C. E. and Griffith, E. H. and Fisher, M. B. and Cole, J. H. and Spang, J. T. and Loboa, E. G.}, year={2016} } @article{nordberg_loboa_2015, title={Our Fat Future: Translating Adipose Stem Cell Therapy}, volume={4}, ISSN={["2157-6580"]}, DOI={10.5966/sctm.2015-0071}, abstractNote={Abstract Summary Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. Significance This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research. }, number={9}, journal={STEM CELLS TRANSLATIONAL MEDICINE}, author={Nordberg, Rachel C. and Loboa, Elizabeth G.}, year={2015}, month={Sep}, pages={974–979} }