Continuous delivery of proteins by engineered cells encapsu-lated in biocompatible polymeric microcapsules is of considerable therapeutic potential. However, this technology has not lived up to expectations due to inadequate cell--matrix interactions and subsequent cell death. In this study we hypoth-esize that the presence of fibronectin in an alginate matrix may enhance the viability and functionality of encapsulated human cord blood-derived mesenchymal stromal cells (MSCs) expressing the human Factor IX (FIX) gene. MSCs were encapsulated in alginate-PLL microcapsules containing 10, 100, or 500 μg/ml fibronectin to ameliorate cell survival. MSCs in microcapsules with 100 and 500 μg/ml fibronectin demonstrated improved cell viability and proliferation and higher FIX secretion compared to MSCs in non-supplemented microcapsules. In contrast, 10 μg/ml fibronectin did not significantly affect the viability and protein secretion from the encapsulated cells. Differentiation studies demonstrated osteogenic (but not chondrogenic or adipogenic) differentiation capability and efficient FIX secretion of the enclosed MSCs in the fibronectin-alginate suspension culture. Thus, the use of recombinant MSCs encapsulated in fibronectin-alginate microcapsules in basal or osteogenic cultures may be of practical use in the treatment of hemophilia B.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3109/21691401.2014.885446 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel Compound HJC0416 Attenuates Hepatic Fibrosis via HSP90/NF-κB-Associated Mechanism.
J Surg Res
December 2024
Department of Surgery, University of Texas Medical Branch, Galveston, Texas. Electronic address:
Introduction: Chronic liver disease is driven by a prolonged wound healing response leading to fibrogenesis, potentially progressing to cirrhosis. Hepatic stellate cells (HSCs) are the primary cells driving hepatic fibrosis because they are major producers of extracellular matrix. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ΚB) pathway is a key regulator of inflammatory signaling, and survival of activated HSCs has been found to be NF-KB dependent.
View Article and Find Full Text PDFOmega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice.
Autoimmunity
November 2020
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
Inhalation of crystalline silica (cSiO) in the workplace is etiologically linked to lupus and other autoimmune diseases. Exposing lupus-prone NZBWF1 mice to respirable cSiO unleashes a vicious cycle of inflammation and cell death in the lung that triggers interferon-regulated gene expression, ectopic lymphoid structure (ELS) development, elevation of local and systemic autoantibodies (AAbs), and glomerulonephritis. However, cSiO-induced inflammation and onset of autoimmunity can be prevented by inclusion of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) into the diet of these mice.
View Article and Find Full Text PDFInhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia.
Mol Med Rep
April 2020
Department of Surgery, Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Intimal hyperplasia (IH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. Activation of HSP90 results in increased cell migration and proliferation.
View Article and Find Full Text PDFDysregulated fibronectin trafficking by Hsp90 inhibition restricts prostate cancer cell invasion.
Sci Rep
February 2018
Adelaide Medical School and Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, SA, 5000, Australia.
The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment.
View Article and Find Full Text PDFHeat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.
Plast Reconstr Surg
September 2015
Seoul, Republic of Korea From the Institute for Human Tissue Restoration, the Department of Plastic and Reconstructive Surgery, Department of Dermatology, the Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine; and the Department of Bioengineering, College of Engineering, Hanyang University.
Background: The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids.
Methods: Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!