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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2165462
Number of pages11
JournalStem Cells International
Volume2016
DOIs
Publication statusPublished - 29 Aug 2016
Externally publishedYes

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