mRNA: A Novel Tool for Cell Reprogramming and Differentiation in Regenerative Medicine| Chapter 3 | Innovations in Biological Science Vol. 9

 

The COVID-19 pandemic generated interest in the medicinal applications of messenger RNA (mRNA). It is expected that mRNA can be applied not only to vaccines but also to regenerative medicine. In the synthesis of mRNA, by-products that do not have a 5' cap structure are generated, and it is generally difficult to remove them. The by-products bind to the host's immune receptors and cause an inflammatory response. To solve this problem, the introduction of chemically modified nucleosides, such as N1-methyl pseudouridine and 5-methylcytidine, has been reported by Karikó and Weissman, opening a path for the practical application of mRNA for vaccines and regenerative medicine. Yamanaka reported the production of induced pluripotent stem cells (iPSCs) by introducing four types of genes using a retrovirus vector. iPSCs are widely used for research on regenerative medicine and the preparation of disease models to screen new drug candidates. Among the Yamanaka factors, Klf4 and c-Myc are oncogenes, and there is a risk of tumor development if these are integrated into genomic DNA. Therefore, regenerative medicine using mRNA, which poses no risk of genome insertion, has attracted attention. Direct reprogramming and protein supplementation therapy using mRNA encoding the reprogramming genes or the specific proteins have been particularly studied in recent years. However, to apply mRNA to regenerative medicine, the further development of delivery technology that can deliver mRNA to specific tissues is strongly demanded. Thus, with the development of research on mRNA synthesis/delivery technology and the accumulation of application examples demonstrating the potential usefulness of mRNA, it is expected that mRNA will have a big impact on regenerative medicine.

 

Author(s) Details

Masahito Inagaki
Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.

 

Please see the book here:- https://doi.org/10.9734/bpi/ibs/v9/1437

Histone Deacetylase Inhibition Restores Expression of Hypoxia-Inducible Protein NDRG1 in Pancreatic Cancer: An Advance Study | Chapter 1 | Highlights on Medicine and Medical Research Vol. 14

 N-myc downstream-regulated gene-1 (NDRG1), a hypoxia-inducible and differentiation-related protein, is a potential biomarker in pancreatic cancer. Because NDRG1 expression is reduced in high-grade tumors, the effects of the differentiating histone deacetylase inhibitor trichostatin A (TSA) in human pancreatic cancer cell lines representing different tumor stages were investigated. Cancer is a genetic disease caused by inherited or sporadic mutations in genes involved in tissue homeostasis, cell cycle control, and apoptosis. TSA was applied to PANC-1 (poorly differentiated) and Capan-1 (moderately to well differentiated) cells. In vitro evaluations included microscopic examinations, colorimetric assays, cell counts, real-time polymerase chain reaction, and Western blotting. PANC-1 cells were treated for four days with 0.5 M TSA. Cell differentiation was restored, proliferation was inhibited, and p21Cip1 protein expression was increased. Trichostatin A increased NDRG1 mRNA and protein levels in normoxia starting on day 1 and increasing by 6-fold by day 4 (P 0.01 at all time points). NDRG1 expression was increased in differentiated cells after 24 hours of hypoxia (P 0.01). Other hypoxia-regulated genes showed an increase in expression.

Conclusions: Histone deacetylase inhibitors have the potential to be a novel epidrug for pancreatic cancer, as they reverse the undifferentiated phenotype, helping patients to overcome resistance and respond better to traditional cytotoxic treatments.

Author (S) Details

Céline Tiffon
Independent Researcher, 50 rue des vignes 92000 Nanterre, Hauts-de-Seine, France.

View Book :- https://stm.bookpi.org/HMMR-V14/article/view/1647