دورية أكاديمية

In Vitro FVIII-Encoding Transgenic Mesenchymal Stem Cells Maintain Successful Coagulation in FVIII-Deficient Plasma Mimicking Hemophilia A

التفاصيل البيبلوغرافية
العنوان: In Vitro FVIII-Encoding Transgenic Mesenchymal Stem Cells Maintain Successful Coagulation in FVIII-Deficient Plasma Mimicking Hemophilia A
المؤلفون: Cansu Hemşinlioğlu, Elif Sibel Aslan, Cihan Tastan, Didem Çakırsoy, Raife Dilek Turan, Utku Seyis, Muhammer Elek, Gözde Sır Karakuş, Ömür Selin Günaydın, Selen Abanuz, Derya Dilek Kançağı, Bulut Yurtsever, Koray Yalçın, Murat Kasap, Ercüment Ovalı
المصدر: Turkish Journal of Hematology, Vol 40, Iss 2, Pp 118-124 (2023)
بيانات النشر: Galenos Publishing House, 2023.
سنة النشر: 2023
المجموعة: LCC:Diseases of the blood and blood-forming organs
مصطلحات موضوعية: factor viii, gene therapy, hemophilia a, lentivirus, mesenchymal stem cells, Diseases of the blood and blood-forming organs, RC633-647.5
الوصف: Objective: Hemophilia A is an X-linked recessive bleeding disorder caused by a deficiency of plasma coagulation factor VIII (FVIII), and it accounts for about 80%-85% of all cases of hemophilia. Plasma-derived therapies or recombinant FVIII concentrates are used to prevent and treat the bleeding symptoms along with FVIIImimicking antibodies. Recently, the European Medicines Agency granted conditional marketing approval for the first gene therapy for hemophilia A. The aim of this study was to determine the effectiveness of coagulation in correcting FVIII deficiency with FVIII-secreting transgenic mesenchymal stem cells (MSCs). Materials and Methods: A lentiviral vector encoding a B domaindeleted FVIII cDNA sequence with CD45R0 truncated (CD45R0t) surface marker was designed to develop a transgenic FVIII-expressing primary cell line by transducing MSCs. The efficacy and functionality of the FVIII secreted from the MSCs was assessed with anti-FVIII ELISA, CD45R0t flow cytometry, FVIII western blot, and mixing test analysis in vitro. Results: The findings of this study showed that the transgenic MSCs maintained persistent FVIII secretion. There was no significant difference in FVIII secretion over time, suggesting stable FVIII expression from the MSCs. The functionality of the FVIII protein secreted in the MSC supernatant was demonstrated by applying a mixing test in coagulation analysis. In the mixing test analysis, FVIIIdeficient human plasma products were mixed with either a saline control or FVIII-secreted MSC supernatant. The mean FVIII level of the saline control group was 0.41±0.03 IU/dL, whereas the mean level was 25.41±33.38 IU/dL in the FVIII-secreting MSC supernatant mixed group (p
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1308-5263
Relation: https://tjh.com.tr/jvi.aspx?pdir=tjh&plng=eng&un=TJH-53911&look4=; https://doaj.org/toc/1308-5263
DOI: 10.4274/tjh.galenos.2023.2022.0318
URL الوصول: https://doaj.org/article/c4d89b70bef242af9b222fa0e01cf281
رقم الأكسشن: edsdoj.4d89b70bef242af9b222fa0e01cf281
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:13085263
DOI:10.4274/tjh.galenos.2023.2022.0318