Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells.
Wen-Hui FangShant KumarGarry McDowellDavid SmithJurek KrupinskiPeter OlahRaid Saleem Al-BaradieMohammad Othman Al-RukbanEugene Bogdan PetcuMark SlevinPublished in: Stem cells international (2016)
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.
Keyphrases
- cell cycle
- stem cells
- mesenchymal stem cells
- drug induced
- drug delivery
- cell proliferation
- cancer therapy
- endothelial cells
- clinical trial
- cell therapy
- protein kinase
- liver failure
- cell cycle arrest
- high glucose
- respiratory failure
- tyrosine kinase
- small molecule
- umbilical cord
- oxidative stress
- bone marrow
- randomized controlled trial
- case report
- wound healing
- intensive care unit
- immune response
- emergency department
- nuclear factor
- endoplasmic reticulum stress
- toll like receptor
- epithelial mesenchymal transition
- induced apoptosis
- phase ii
- adverse drug
- study protocol
- placebo controlled