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Role of iPSCs in Disease Modeling: Gaucher Disease and Related Disorders
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Daniel K. Borger, Elma Aflaki, Ellen Sidransky
In addition to dopaminergic neurons, Panicker et al. (9) and Tiscornia et al. (10) also differentiated GD iPSCs into macrophages, by way of monocytes. Both studies used CD14 and CD163 as markers of macrophage differentiation, with Panicker et al. (9) including CD68 and Tiscornia et al. (10) including CD11b and CD33. In all cases, control and GD iPSC lines produced macrophages at similar efficiencies. To further confirm that reduced GCase activity does not impact the iPSC differentiation process, Tiscornia et al. (10) used a lentiviral vector to transduce their type 2 GD iPSC line with wild-type GBA1, which restored GCase activity to control levels. They then compared the differentiation efficiency of both transduced and nontransduced lines and found that both produced cells with similar marker patterns upon differentiation to macrophages (10). Taken together, these results suggest that the metabolic defect in GD has little to no effect on either the reprogramming or the differentiation processes.
Deep Learning and Economic Prospects in Medical and Pharmaceutical Biotechnology
Published in Hajiya Mairo Inuwa, Ifeoma Maureen Ezeonu, Charles Oluwaseun Adetunji, Emmanuel Olufemi Ekundayo, Abubakar Gidado, Abdulrazak B. Ibrahim, Benjamin Ewa Ubi, Medical Biotechnology, Biopharmaceutics, Forensic Science and Bioinformatics, 2022
Charles Oluwaseun Adetunji, Kingsley Eghonghon Ukhurebor, Olugbemi Tope Olaniyan, Juliana Bunmi Adetunji, Gloria E. Okotie, Julius Kola Oloke
Guoyao and Fuller (2019) revealed that biotechnology-based breeding is the needed breakthrough to meet the increasing response for genetic traits and demand of quality pork protein. They grouped gene cloning by identical gene or genetic engineering to generate modified microorganisms or animals. It is known that cloning conserves the genetic trait or breed, while recombinant DNA technology for bioengineering uses multiple sources of genes. Genome editing utilizes insertion, deletion, and silencing to produce genetically modified products. Many tools of gene editing are presently deployed for biotechnological processes such as zinc finger nuclease, clustered regularly interspaced short palindromic repeats-associated nuclease-9 and transcription activator-like effector nuclease targeting cell, bacteriophages or plasmid via transfection like electroporation, lipid-based ligands, microinjection, and nucleofection. The authors revealed that the use of genetically modified pigs has been able to produce bacterial phytase, growth hormone, C. elegans fatty acid desaturases, fungal carbohydrases, uncoupling protein-1; lack of myostatin, CD163 or α-1,3-galactosyltransferase; and concluded that biotechnology provides opportunity to improve efficiency of swine generation plus develop a substitute to antibiotics in the nearest future. Fang et al. (2016) revealed that with the advancement in molecular biology tools, more development is being seen in DNA-based technologies to provide and promote quality and safe crop breeding products, increase agricultural output, and equally protecting the eco-environment. Hence, their role in modern day agro-science sector is becoming more important. The authors in their study described the utilization of biotechnological skills and bioengineering to improve agricultural yield such as molecular markers, genetic engineering, and genome editing.
Macrophage Targeting: A Promising Strategy for Delivery of Chemotherapeutics in Leishmaniasis and Other Visceral Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Jaya Gopal Meher, Pankaj K. Singh, Yuvraj Singh, Mohini Chaurasia, Anita Singh, Manish K. Chourasia
Another study by Melgert et al. shows kupffer cells targeting of anti-inflammatory drug dexamethasone (Melgert et al., 2001). The researchers realized that kupffer cells are one of the vital players in pathogenesis of inflammatory liver diseases, which if not taken care of may lead to fibrosis. Accordingly, they have coupled mannosylated albumin with dexamethasone and examined its targeting efficiency to kupffer cells in liver employing organ cultures as well as fibrosis induced by bile duct ligation in rats. Their experimental findings suggested that the mannosylated albumin-dexamethasone conjugate could be selectively taken-up by kupffer cells in fibrotic and healthy rats. Significant reduction in intrahepatic ROS in animals and decrease in TNF-alpha production in in-vitro conditions supported better targeting of drug to target cells. So this combination could be treated as a suitable liver macrophage targeting alternative for drug delivery. Apart from inflammatory liver diseases, non-alcoholic fatty liver diseases are also one of the leading causes of death in human beings with chronic liver diseases. This has risen because of bad food habits such as consumption of high caloric carbohydrates which may also lead to non-alcoholic steatohepatitis. Researchers have shown that lipogenetic effects of fructose (high caloric intake) and activation of liver macrophages due to endotoxins are major reasons for development and progression of these liver diseases. In light of these findings, Svendsen et al. investigated kupffer cell targeting by using an anti-CD163-IgG-dexamethasone conjugate (Svendsen et al., 2017). They intended to target the hemoglobin scavenger receptor CD163 in Kupffer cells. A low dose of anti-CD163-IgG-dexamethasone was administered to rats on a high-fructose diet, and within few weeks a significant reduction in hepatocyte ballooning, glycogen deposition, inflammation as well as fibrosis was observed. Dexamethasone alone or dexamethasone conjugated to control-IgG could not produce such therapeutic effect in rats.
Docosahexaenoic acid impacts macrophage phenotype subsets and phagolysosomal membrane permeability with particle exposure
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Paige Fletcher, Raymond F. Hamilton, Joseph F. Rhoderick, James J. Pestka, Andrij Holian
The ability of AM to phagocytose these particles affected their LMP in vitro which differed between the various phenotypes, indicated that the phagolysosomal membrane within each of the phenotypes was altered. One possible explanation might be differences in scavenger receptors between the various macrophage phenotypes which subsequently affect how they respond to phagocytosing particles. Canton, Neculai, and Grinstein (2013) noted that there is an increase of CD36 in M1 macrophages and an elevation in both SR-A1 and CD163 in M2a macrophages. Another study; Rozovski et al. (2018) reported that STAT3 induces CD36 expression in a chronic lymphocytic leukemia model and that fatty acid uptake is facilitated by STAT3-mediated expression of CD36. In a gastric cancer model, STAT3 was an important regulator of CD163 (Cheng et al. 2017). In the current in vitro studies, increased particle uptake of MWCNT was found when exposed to DHA in M2a and SiO2 in M2a, M2b, and M2c suggesting that the other M2 subsets may vary in their scavenger receptors which might be altered by STAT3. While scavenger receptors are known to be responsible for the uptake of SiO2 (Hamilton et al. 2006), scavenger receptors for MWCNT exposure are less well-described. There is also the possibility that fatty acid incorporation into the membranes occurs differently between macrophage phenotypes. The type of particle exposure may also potentially alter these expressions depending upon differences in physiochemical properties as indicated above. The impacts of DHA on AM in vitro were mixed yet DHA treatment appeared to exert a beneficial effect after a 24-hr particle exposure specifically in the M2c phenotype. However, the in vivo 24-hr particle exposure study showed a different outcome.