Gene transfer experiments in nonhuman primates have been shown to be predictive of success in human clinical gene therapy trials. In most nonhuman primate studies, hematopoietic stem cells (HSCs) collected from the peripheral blood or bone marrow after administration of granulocyte colony-stimulating factor (G-CSF) + stem cell factor (SCF) have been used as targets, but this cytokine combination is not generally available for clinical use, and the optimum target cell population has not been systematically studied. In our current study we tested the retroviral transduction efficiency of rhesus macaque peripheral blood CD34(+) cells collected after administration of different cytokine mobilization regimens, directly comparing G-CSF+SCF versus G-CSF alone or G-CSF+Flt3-L in competitive repopulation assays. Vector supernatant was added daily for 96 hours in the presence of stimulatory cytokines. The transduction efficiency of HSCs as assessed by in vitro colony-forming assays was equivalent in all 5 animals tested, but the in vivo levels of mononuclear cell and granulocyte marking was higher at all time points derived from target CD34(+) cells collected after G-CSF+SCF mobilization compared with target cells collected after G-CSF (n = 3) or G-CSF+Flt3-L (n = 2) mobilization. In 3 of the animals long-term marking levels of 5% to 25% were achieved, but originating only from the G-CSF+SCF-mobilized target cells. Transduction efficiency of HSCs collected by different mobilization regimens can vary significantly and is superior with G-CSF+SCF administration. The difference in transduction efficiency of HSCs collected from different sources should be considered whenever planning clinical gene therapy trials and should preferably be tested directly in comparative studies.
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http://dx.doi.org/10.1182/blood-2002-08-2663 | DOI Listing |
Cell Prolif
December 2024
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The recent advancements in cancer immunotherapy have spotlighted the potential of natural killer (NK) cells, particularly chimeric antigen receptor (CAR)-transduced NK cells. These cells, pivotal in innate immunity, offer a rapid and potent response against cancer cells and pathogens without the need for prior sensitization or recognition of peptide antigens. Although NK cell genetic modification is evolving, the viral transduction method continues to be inefficient and fraught with risks, often resulting in cytotoxic outcomes and the possibility of insertional mutagenesis.
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December 2024
Naval Special Medical Center, Naval Medical University, Shanghai, 200433, China.
Superoxide dismutase (SOD) plays important roles in the balance of oxidation and antioxidation in body mostly by scavenging superoxide anion free radicals (O). Previously, we reported a novel Cu/Zn SOD from jellyfish Cyanea capillata, named CcSOD1, which exhibited excellent SOD activity and high stability. TAT peptide is a common type of cell penetrating peptides (CPPs) that efficiently deliver extracellular biomacromolecules into cytoplasm.
View Article and Find Full Text PDFMetabolites
December 2024
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya St., 3, Pushchino 142290, Russia.
Background: Acetyl phosphate (AcP) is a microbial intermediate involved in the central bacterial metabolism. In bacteria, it also functions as a donor of acetyl and phosphoryl groups in the nonenzymatic protein acetylation and signal transduction. In host, AcP was detected as an intermediate of the pyruvate dehydrogenase complex, and its appearance in the blood was considered as an indication of mitochondrial breakdown.
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December 2024
Marine Medical Research and Development Centre, Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China.
Heat stress poses a significant challenge to animal husbandry, contributing to oxidative stress, intestinal mucosal injury, and apoptosis, which severely impact animal health, growth, and production efficiency. The development of safe, sustainable, and naturally derived solutions to mitigate these effects is critical for advancing sustainable agricultural practices. Butyrolactone-I (BTL-I), a bioactive compound derived from deep-sea fungi (Aspergillus), shows promise as a functional feed additive to combat heat stress in animals.
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December 2024
State Key Laboratory of Crop Stress Resistance and High-Efficiency Production, College of Agronomy, Northwest A&F University, Yangling, China.
Cytokinin signalling plays both positive and negative roles in plant resistance to pathogens. It is not clear whether the role of cytokinin changes at the different stages of pathogen infection. Arabidopsis thaliana sequentially exhibits distinct root morphological symptoms during Ralstonia solanacearum infection, which offers a good system to investigate function of cytokinin in the whole pathogen infection process.
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