Search

Your search keyword '"Kostina, Aleksandra"' showing total 24 results
Start Over Author "Kostina, Aleksandra"
24 results on '"Kostina, Aleksandra"'

2. Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease

Author

Theodoris, Christina V, Zhou, Ping, Liu, Lei, Zhang, Yu, Nishino, Tomohiro, Huang, Yu, Kostina, Aleksandra, Ranade, Sanjeev S, Gifford, Casey A, Uspenskiy, Vladimir, Malashicheva, Anna, Ding, Sheng, and Srivastava, Deepak

Subjects
Heart Disease, Biotechnology, Stem Cell Research, Rare Diseases, Stem Cell Research - Induced Pluripotent Stem Cell, Cardiovascular, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Orphan Drug, Genetics, Regenerative Medicine, Aetiology, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Good Health and Well Being, Algorithms, Animals, Aortic Valve, Aortic Valve Disease, Aortic Valve Stenosis, Calcinosis, Disease Models, Animal, Drug Discovery, Drug Evaluation, Preclinical, Gene Expression Regulation, Gene Regulatory Networks, Haploinsufficiency, Humans, Induced Pluripotent Stem Cells, Machine Learning, Mice, Inbred C57BL, Nitriles, RNA-Seq, Receptor, Notch1, Small Molecule Libraries, Thiazoles, General Science & Technology
Abstract

Mapping the gene-regulatory networks dysregulated in human disease would allow the design of network-correcting therapies that treat the core disease mechanism. However, small molecules are traditionally screened for their effects on one to several outputs at most, biasing discovery and limiting the likelihood of true disease-modifying drug candidates. Here, we developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell (iPSC) disease model of a common form of heart disease involving the aortic valve (AV). Gene network correction by the most efficacious therapeutic candidate, XCT790, generalized to patient-derived primary AV cells and was sufficient to prevent and treat AV disease in vivo in a mouse model. This strategy, made feasible by human iPSC technology, network analysis, and machine learning, may represent an effective path for drug discovery.

Published
2021

3. ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development

Author

Kostina, Aleksandra, primary, Lewis-Israeli, Yonatan R., additional, Abdelhamid, Mishref, additional, Gabalski, Mitchell A., additional, Kiselev, Artem, additional, Volmert, Brett D., additional, Lankerd, Haley, additional, Huang, Amanda R., additional, Wasserman, Aaron H., additional, Lydic, Todd, additional, Chan, Christina, additional, Park, Sangbum, additional, Olomu, Isoken, additional, and Aguirre, Aitor, additional

Published
2024
Full Text
View/download PDF

6. Human heart organoids: current applications and future perspectives.

Author

Kostina, Aleksandra, Volmert, Brett, and Aguirre, Aitor

Subjects
ORGANOIDS, HEART, DRUG toxicity, VENTRICULAR septal defects
Abstract

Human heart organoids (hHOs) have emerged as powerful tools in cardiovascular research. These three-dimensional structures mimic the architecture and function of real organs, providing a more physiologically relevant model for studying diseases and developing therapies. hHOs can be generated from human pluripotent stem cells and have been successfully used to model congenital heart disease and investigate the effects of teratogens, environmental factors, and genetic mutations. They also offer potential in drug discovery, cardiotoxicity testing, disease modeling, precision medicine, regenerative medicine, and reducing reliance on animal models. However, there are still limitations and challenges that need to be addressed to improve these models. [Extracted from the article]

Published
2024
Full Text
View/download PDF

7. A patterned human heart tube organoid model generated by pluripotent stem cell self-assembly

Author

Volmert, Brett, primary, Riggs, Ashlin, additional, Wang, Fei, additional, Juhong, Aniwat, additional, Kiselev, Artem, additional, Kostina, Aleksandra, additional, O’Hern, Colin, additional, Muniyandi, Priyadharshni, additional, Wasserman, Aaron, additional, Huang, Amanda, additional, Lewis-Israeli, Yonatan, additional, Park, Sangbum, additional, Qiu, Zhen, additional, Zhou, Chao, additional, and Aguirre, Aitor, additional

Published
2022
Full Text
View/download PDF

13. Generation of two iPSC lines (FAMRCi007-A and FAMRCi007-B) from patient with Emery–Dreifuss muscular dystrophy and heart rhythm abnormalities carrying genetic variant LMNA p.Arg249Gln

Author

Perepelina, Kseniya, primary, Kostina, Aleksandra, additional, Klauzen, Polina, additional, Khudiakov, Aleksandr, additional, Rabino, Martina, additional, Crasto, Silvia, additional, Zlotina, Anna, additional, Fomicheva, Yulia, additional, Sergushichev, Alexey, additional, Oganesian, Mari, additional, Dmitriev, Alexander, additional, Kostareva, Anna, additional, Di Pasquale, Elisa, additional, and Malashicheva, Anna, additional

Published
2020
Full Text
View/download PDF

19. Inflammation and Mechanical Stress Stimulate Osteogenic Differentiation of Human Aortic Valve Interstitial Cells

Author

Bogdanova, Maria, primary, Kostina, Aleksandra, additional, Zihlavnikova Enayati, Katarina, additional, Zabirnyk, Arsenii, additional, Malashicheva, Anna, additional, Stensløkken, Kåre-Olav, additional, Sullivan, Gareth John, additional, Kaljusto, Mari-Liis, additional, Kvitting, John-Peder Escobar, additional, Kostareva, Anna, additional, Vaage, Jarle, additional, and Rutkovskiy, Arkady, additional

Published
2018
Full Text
View/download PDF

20. Notch, BMP and WNT/β-catenin network is impaired in endothelial cells of the patients with thoracic aortic aneurysm

Author

Kostina, Aleksandra, primary, Bjork, Hanna, additional, Ignatieva, Elena, additional, Irtyuga, Olga, additional, Uspensky, Vladimir, additional, Semenova, Daria, additional, Maleki, Shohreh, additional, Tomilin, Alexey, additional, Moiseeva, Olga, additional, Franco-Cereceda, Anders, additional, Gordeev, Mikhail, additional, Faggian, Giuseppe, additional, Kostareva, Anna, additional, Eriksson, Per, additional, and Malashicheva, Anna, additional

Published
2018
Full Text
View/download PDF

21. Dose-dependent mechanism of Notch action in promoting osteogenic differentiation of mesenchymal stem cells.

Author

Semenova, Daria, Bogdanova, Maria, Kostina, Aleksandra, Golovkin, Alexey, Kostareva, Anna, and Malashicheva, Anna

Subjects
MESENCHYMAL stem cell differentiation, NOTCH signaling pathway, BIOCHEMICAL mechanism of action, MESENCHYMAL stem cells, STEM cells, FAT cells, PROGENITOR cells, OSTEOBLASTS
Abstract

Osteogenic differentiation is a tightly regulated process realized by progenitor cell osteoblasts. Notch signaling pathway plays a critical role in skeletal development and bone remodeling. Controversial data exist regarding the role of Notch activation in promoting or preventing osteogenic differentiation. This study aims to investigate the effect of several Notch components and their dosage on osteogenic differentiation of mesenchymal stem cells of adipose tissue. Osteogenic differentiation was induced in the presence of either of Notch components (NICD, Jag1, Dll1, Dll4) dosed by lentiviral transduction. We show that osteogenic differentiation was increased by NICD and Jag1 transduction in a dose-dependent manner; however, a high dosage of both NICD and Jag1 decreased the efficiency of osteogenic differentiation. NICD dose-dependently increased activity of the CSL luciferase reporter but a high dosage of NICD caused a decrease in the activity of the reporter. A high dosage of both Notch components NICD and Jag1 induced apoptosis. In co-culture experiments where only half of the cells were transduced with either NICD or Jag1, only NICD increased osteogenic differentiation according to the dosage, while Jag1-transduced cells differentiated almost equally independently on dosage. In conclusion, activation of Notch promotes osteogenic differentiation in a tissue-specific dose-dependent manner; both NICD and Jag1 are able to increase osteogenic potential but at moderate doses only and a high dosage of Notch activation is detrimental to osteogenic differentiation. This result might be especially important when considering possibilities of using Notch activation to promote osteogenesis in clinical applications to bone repair. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

22. Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve

Author

Kostina, Aleksandra S., primary, Uspensky, Vladimir Е., additional, Irtyuga, Olga B., additional, Ignatieva, Elena V., additional, Freylikhman, Olga, additional, Gavriliuk, Natalia D., additional, Moiseeva, Olga M., additional, Zhuk, Sergey, additional, Tomilin, Alexey, additional, Kostareva, Аnna А., additional, and Malashicheva, Anna B., additional

Published
2016
Full Text
View/download PDF

23. Phenotypic and Functional Changes of Endothelial and Smooth Muscle Cells in Thoracic Aortic Aneurysms

Author

Malashicheva, Anna, primary, Kostina, Daria, additional, Kostina, Aleksandra, additional, Irtyuga, Olga, additional, Voronkina, Irina, additional, Smagina, Larisa, additional, Ignatieva, Elena, additional, Gavriliuk, Natalia, additional, Uspensky, Vladimir, additional, Moiseeva, Olga, additional, Vaage, Jarle, additional, and Kostareva, Anna, additional

Published
2016
Full Text
View/download PDF

24. ER stress and lipid imbalance drive embryonic cardiomyopathy in a human heart organoid model of pregestational diabetes.

Author

Kostina A, Lewis-Israeli YR, Abdelhamid M, Gabalski MA, Volmert BD, Lankerd H, Huang AR, Wasserman AH, Lydic T, Chan C, Olomu I, and Aguirre A

Abstract

Congenital heart defects constitute the most common birth defect in humans, affecting approximately 1% of all live births. The incidence of congenital heart defects is exacerbated by maternal conditions, such as diabetes during the first trimester. Our ability to mechanistically understand these disorders is severely limited by the lack of human models and the inaccessibility to human tissue at relevant stages. Here, we used an advanced human heart organoid model that recapitulates complex aspects of heart development during the first trimester to model the effects of pregestational diabetes in the human embryonic heart. We observed that heart organoids in diabetic conditions develop pathophysiological hallmarks like those previously reported in mouse and human studies, including ROS-mediated stress and cardiomyocyte hypertrophy, among others. Single cell RNA-seq revealed cardiac cell type specific-dysfunction affecting epicardial and cardiomyocyte populations, and suggested alterations in endoplasmic reticulum function and very long chain fatty acid lipid metabolism. Confocal imaging and LC-MS lipidomics confirmed our observations and showed that dyslipidemia was mediated by fatty acid desaturase 2 (FADS2) mRNA decay dependent on IRE1-RIDD signaling. We also found that the effects of pregestational diabetes could be reversed to a significant extent using drug interventions targeting either IRE1 or restoring healthy lipid levels within organoids, opening the door to new preventative and therapeutic strategies in humans.

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results