Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells

The potential use of stem cells as therapeutics in disease has gained momentum over the last few years and recently phase-I clinical trials have shown favourable results in treatment of a small cohort of acute stroke patients. Similarly, they have been used in preclinical models drug-loaded for the...

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Main Authors: Wen-Hui Fang, Shant Kumar, Garry McDowell, David Smith, Jurek Krupinski, Peter Olah, Raid Saleem Al-Baradie, Mohammad Othman Al-Rukban, Eugene Bogdan Petcu, Mark Slevin
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/2165462
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author Wen-Hui Fang
Shant Kumar
Garry McDowell
David Smith
Jurek Krupinski
Peter Olah
Raid Saleem Al-Baradie
Mohammad Othman Al-Rukban
Eugene Bogdan Petcu
Mark Slevin
author_facet Wen-Hui Fang
Shant Kumar
Garry McDowell
David Smith
Jurek Krupinski
Peter Olah
Raid Saleem Al-Baradie
Mohammad Othman Al-Rukban
Eugene Bogdan Petcu
Mark Slevin
author_sort Wen-Hui Fang
collection DOAJ
description The potential use of stem cells as therapeutics in disease has gained momentum over the last few years and recently phase-I clinical trials have shown favourable results in treatment of a small cohort of acute stroke patients. Similarly, they have been used in preclinical models drug-loaded for the effective treatment of solid tumours. Here we have characterized uptake and release of a novel p5-cyclin-dependent kinase 5 (CDK5) inhibitory peptide by mesenchymal stem cells and showed release levels capable of blocking aberrant cyclin-dependent kinase 5 (CDK5) signaling pathways, through phosphorylation of cyclin-dependent kinase 5 (CDK5) and p53. These pathways represent the major acute mechanism stimulating apoptosis after stroke and hence its modulation could benefit patient recovery. This work indicates a potential use for drug-loaded stem cells as delivery vehicles for stroke therapeutics and in addition as anticancer receptacles particularly, if a targeting and/or holding mechanism can be defined.
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institution DOAJ
issn 1687-966X
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language English
publishDate 2016-01-01
publisher Wiley
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series Stem Cells International
spelling doaj-art-cbe061aee5d345e299cb07af26eb8a4c2025-08-20T03:23:37ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/21654622165462Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial CellsWen-Hui Fang0Shant Kumar1Garry McDowell2David Smith3Jurek Krupinski4Peter Olah5Raid Saleem Al-Baradie6Mohammad Othman Al-Rukban7Eugene Bogdan Petcu8Mark Slevin9School of Healthcare Science, Manchester Metropolitan University, Manchester, UKSchool of Healthcare Science, Manchester Metropolitan University, Manchester, UKSchool of Healthcare Science, Manchester Metropolitan University, Manchester, UKSchool of Healthcare Science, Manchester Metropolitan University, Manchester, UKDepartment of Neurology, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, SpainUniversity of Medicine and Pharmacy, Tirgu Mures, RomaniaDepartment of Medical Laboratories, College of Applied Medical Sciences, Majmaah University, Al Majma’ah, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Majmaah University, Al Majma’ah, Saudi ArabiaGriffith University School of Medicine and Queensland Eye Institute, Griffith University, Nathan, QLD, AustraliaSchool of Healthcare Science, Manchester Metropolitan University, Manchester, UKThe potential use of stem cells as therapeutics in disease has gained momentum over the last few years and recently phase-I clinical trials have shown favourable results in treatment of a small cohort of acute stroke patients. Similarly, they have been used in preclinical models drug-loaded for the effective treatment of solid tumours. Here we have characterized uptake and release of a novel p5-cyclin-dependent kinase 5 (CDK5) inhibitory peptide by mesenchymal stem cells and showed release levels capable of blocking aberrant cyclin-dependent kinase 5 (CDK5) signaling pathways, through phosphorylation of cyclin-dependent kinase 5 (CDK5) and p53. These pathways represent the major acute mechanism stimulating apoptosis after stroke and hence its modulation could benefit patient recovery. This work indicates a potential use for drug-loaded stem cells as delivery vehicles for stroke therapeutics and in addition as anticancer receptacles particularly, if a targeting and/or holding mechanism can be defined.http://dx.doi.org/10.1155/2016/2165462
spellingShingle Wen-Hui Fang
Shant Kumar
Garry McDowell
David Smith
Jurek Krupinski
Peter Olah
Raid Saleem Al-Baradie
Mohammad Othman Al-Rukban
Eugene Bogdan Petcu
Mark Slevin
Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells
Stem Cells International
title Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells
title_full Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells
title_fullStr Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells
title_full_unstemmed Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells
title_short Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells
title_sort mesenchymal stem cells loaded with p5 derived from cdk5 activator p35 inhibit calcium induced cdk5 activation in endothelial cells
url http://dx.doi.org/10.1155/2016/2165462
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