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Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo

The TNF-related apoptosis-inducing ligand (TRAIL) could induce apoptosis of leukemic cells, while showed no cytotoxic effect on normal cells. One of the limitations for application of recombinant TRAIL (rhTRAIL) in leukemia treatment is that the serum half-life of this protein is short. Gene deliver...

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Autores principales: Chen, Fangshan, Zhong, Xianmei, Dai, Qian, Li, Kuo, Zhang, Wei, Wang, Jie, Zhao, Yueshui, Shen, Jing, Xiao, Zhangang, Xing, Hongyun, Li, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693801/
https://www.ncbi.nlm.nih.gov/pubmed/36422522
http://dx.doi.org/10.3390/ph15111391
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author Chen, Fangshan
Zhong, Xianmei
Dai, Qian
Li, Kuo
Zhang, Wei
Wang, Jie
Zhao, Yueshui
Shen, Jing
Xiao, Zhangang
Xing, Hongyun
Li, Jing
author_facet Chen, Fangshan
Zhong, Xianmei
Dai, Qian
Li, Kuo
Zhang, Wei
Wang, Jie
Zhao, Yueshui
Shen, Jing
Xiao, Zhangang
Xing, Hongyun
Li, Jing
author_sort Chen, Fangshan
collection PubMed
description The TNF-related apoptosis-inducing ligand (TRAIL) could induce apoptosis of leukemic cells, while showed no cytotoxic effect on normal cells. One of the limitations for application of recombinant TRAIL (rhTRAIL) in leukemia treatment is that the serum half-life of this protein is short. Gene delivery is a good strategy to prolong the half-life of TRAIL. In this study, we genetically engineered umbilical cord-MSCs to continuously express and secrete soluble TRAIL (MSC-sTRAIL), to investigate the effects of MSC-sTRAIL on B-cell acute lymphocytic leukemia (B-ALL) cells. In vitro, MSC-sTRAIL significantly inhibited the proliferation of B-ALL cells by suppressing PI3K/AKT and MEK/ERK signaling pathways, and induced apoptosis of B-ALL cells via the caspase cascade-mediated pathway and mitochondrial-mediated pathway. In vivo, MSC-sTRAIL dramatically inhibited B-ALL cell growth. Meanwhile, B-ALL-induced splenic and renal injuries were significantly alleviated after MSC-sTRAIL treatment. Moreover, the serum levels of MSC-secreted sTRAIL were still high in MSC-sTRAIL treated mice, indicating an extended half-life of sTRAIL. Our study suggests that MSC delivered-TRAIL secretion is a potential therapeutic strategy for B-ALL treatment.
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spelling pubmed-96938012022-11-26 Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo Chen, Fangshan Zhong, Xianmei Dai, Qian Li, Kuo Zhang, Wei Wang, Jie Zhao, Yueshui Shen, Jing Xiao, Zhangang Xing, Hongyun Li, Jing Pharmaceuticals (Basel) Article The TNF-related apoptosis-inducing ligand (TRAIL) could induce apoptosis of leukemic cells, while showed no cytotoxic effect on normal cells. One of the limitations for application of recombinant TRAIL (rhTRAIL) in leukemia treatment is that the serum half-life of this protein is short. Gene delivery is a good strategy to prolong the half-life of TRAIL. In this study, we genetically engineered umbilical cord-MSCs to continuously express and secrete soluble TRAIL (MSC-sTRAIL), to investigate the effects of MSC-sTRAIL on B-cell acute lymphocytic leukemia (B-ALL) cells. In vitro, MSC-sTRAIL significantly inhibited the proliferation of B-ALL cells by suppressing PI3K/AKT and MEK/ERK signaling pathways, and induced apoptosis of B-ALL cells via the caspase cascade-mediated pathway and mitochondrial-mediated pathway. In vivo, MSC-sTRAIL dramatically inhibited B-ALL cell growth. Meanwhile, B-ALL-induced splenic and renal injuries were significantly alleviated after MSC-sTRAIL treatment. Moreover, the serum levels of MSC-secreted sTRAIL were still high in MSC-sTRAIL treated mice, indicating an extended half-life of sTRAIL. Our study suggests that MSC delivered-TRAIL secretion is a potential therapeutic strategy for B-ALL treatment. MDPI 2022-11-11 /pmc/articles/PMC9693801/ /pubmed/36422522 http://dx.doi.org/10.3390/ph15111391 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Fangshan
Zhong, Xianmei
Dai, Qian
Li, Kuo
Zhang, Wei
Wang, Jie
Zhao, Yueshui
Shen, Jing
Xiao, Zhangang
Xing, Hongyun
Li, Jing
Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
title Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
title_full Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
title_fullStr Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
title_full_unstemmed Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
title_short Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
title_sort human umbilical cord msc delivered-soluble trail inhibits the proliferation and promotes apoptosis of b-all cell in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693801/
https://www.ncbi.nlm.nih.gov/pubmed/36422522
http://dx.doi.org/10.3390/ph15111391
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