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Stem Cells Int. 2016;2016:2165462. doi: 10.1155/2016/2165462. Epub 2016 Aug 29.

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

Stem cells international

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

Affiliations

  1. School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.
  2. Department of Neurology, Hospital Universitari MĂștua de Terrassa, Terrassa, Barcelona, Spain.
  3. University of Medicine and Pharmacy, Tirgu Mures, Romania.
  4. Department of Medical Laboratories, College of Applied Medical Sciences, Majmaah University, Al Majma'ah, Saudi Arabia.
  5. Griffith University School of Medicine and Queensland Eye Institute, Griffith University, Nathan, QLD, Australia.
  6. School of Healthcare Science, Manchester Metropolitan University, Manchester, UK; University of Medicine and Pharmacy, Tirgu Mures, Romania.

PMID: 27651795 PMCID: PMC5019892 DOI: 10.1155/2016/2165462

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.

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