Implantation of microencapsulated recombinant cells is an alternative approach to gene therapy. These genetically-engineered cells enclosed in microcapsules to deliver therapeutic recombinant products have been effective in treating several murine models of human diseases. However, the most commonly used microcapsules fabricated from alginate ionically cross-linked with calcium suffer from loss of long-term mechanical stability. We now report on a method to improve their stability by introducing additional polymers to provide covalent linkages via photopolymerization. Vinyl monomers and a photoinitiator were allowed to diffuse into the initially formed calcium-alginate microcapsules. In situ photopolymerization in the presence of sodium acrylate and N-vinylpyrrolidone substantially enhanced their mechanical strength. After four months of storage in saline, > 70% of these capsules remained intact in the osmotic pressure test, while the un-modified alginate microcapsules totally disintegrated. Tests of their permeability to polyethylene glycol of different molecular weight and their ability to support cell survival showed that these properties remained unaffected by the photopolymerization. Hence, these microcapsules modified by adding a network of vinyl polymers are promising candidates to use for long-term delivery of recombinant gene products in this cell-based method of gene therapy.
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http://dx.doi.org/10.1163/1568562052843302 | DOI Listing |
Neurology
February 2025
Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong, People's Republic of China.
Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.
Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Genetic Engineering, School of Life Sciences, Liver Cancer Institute of Zhongshan Hospital, Fudan University, Shanghai 200438, China.
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named (), harboring a mutation in the - () gene. Loss of leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration.
View Article and Find Full Text PDFPLoS One
January 2025
Cell Therapy Center, The University of Jordan, Amman, Jordan.
Background: Hypoxia in tumor cells is linked to increased drug resistance and more aggressive behavior. In pancreatic cancer, the tumor microenvironment is notably hypoxic and exhibits strong immunosuppressive properties. Given that immunotherapy is now approved for pancreatic cancer treatment, further understanding of how pancreatic tumor cell hypoxia influences T-cell cytotoxicityis essential.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Renal osteodystrophy is commonly seen in patients with chronic kidney disease (CKD) due to disrupted mineral homeostasis. Given the impaired renal function in these patients, common anti-resorptive agents, including bisphosphonates, must be used with caution or even contraindicated. Therefore, an alternative therapy without renal burden to combat renal osteodystrophy is urgently needed.
View Article and Find Full Text PDFInflammation
January 2025
Department of Nephrology, the First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu, 233000, Anhui Province, China.
Primary membranous nephropathy (PMN) is a prevalent renal disorder characterized by immune-mediated damage to the glomerular basement membrane, with recent studies highlighting the significant role of pyroptosis in its progression. In this study, we investigate the molecular mechanisms underlying PMN, focusing on the role of Tumor necrosis factor receptor-associated factor 6 (TRAF6) in promoting disease advancement. Specifically, we examine how TRAF6 facilitates PMN progression by inducing the ubiquitination of Transforming growth factor-beta-activated kinase 1 (TAK1), which in turn activates the Gasdermin D (GSDMD)/Caspase-1 axis, leading to podocyte pyroptosis.
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