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.
Highlights
Despite all recent advances in ischemic stroke research, treatments and recovery rates of patients have not been improved significantly [1]
Cells were grown in stem cells medium (SCM) comprised of 80% Iscove’s modified Dulbecco’s medium (IMDM; Sigma-Aldrich) containing 5% fetal bovine serum (FBS; Sigma-Aldrich), 10% NeuroCult medium (Stem Cell Technologies), and 10% endothelial basal medium (EBM) (Lonza) in a humidified incubator with 5% CO2 at 37∘C
Uptake and Release of p5 by Human adipose-derived mesenchymal stem cells (hADMSCs). p5 is a 24-residue peptide derived from p35, the cyclin-dependent kinase 5 (CDK5) activator
Summary
Despite all recent advances in ischemic stroke research, treatments and recovery rates of patients have not been improved significantly [1]. In contrast to the treatment of diseases such as diabetes and Parkinson’s disease where restricted populations are lost, multiple cell types are lost in stroke and it will be important to repair both blood vessels (endothelial cells, smooth muscle cells, and pericytes) and neurons and glial cells [3,4,5]. Another important distinction is that stroke is an acute injury limited in time, which might make the brain more hospitable to transplantation than in other diseases. Mesenchymal stem cells (MSCs, called mesenchymal stromal cells) have the advantage of being relatively easy to propagate in vitro and implantation of autologous MSCs into patients has fewer ethical problems and is not subject to alloimmunization and may represent an ideal candidate for cellular therapies [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
