p5 Peptide-Loaded Human Adipose-Derived Mesenchymal Stem Cells Promote Neurological Recovery After Focal Cerebral Ischemia in a Rat Model

Arjun Paudyal, Flavia Semida Ghinea, Mircea Popescu Driga, Wen-hui Fang, Giulio Alessandri, Laura Combes, Hans Degens, Mark Slevin, Dirk M. Hermann, Aurel Popa-wagner

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Abstract

Adipose-derived mesenchymal stem cells markedly attenuated brain infarct size and improved neurological function in rats. The mechanisms for neuronal cell death have previously been defined in stress states to suggest that an influx of calcium ions into the neurons activates calpain cleavage of p35 into p25 forming a hyperactive complex that induces cell death. Now we report that p5, a 24-residue peptide derived from p35, offers protection to neurons and endothelial cells in vitro. In vivo administration of human adipose-derived mesenchymal stem cells (hADMSCs) loaded with this therapeutic peptide to post-stroke rats had no effect on the infarct volume. Nevertheless, the treatment led to improvement in functional recovery in spatial learning and memory (water maze), bilateral coordination and sensorimotor function (rotating pole), and asymmetry of forelimb usage (cylinder test). However, the treatment may not impact on cutaneous sensitivity (adhesive tape removal test). In addition, the double immunofluorescence with human cell-specific antibodies revealed that the number of surviving transplanted cells was higher in the peri-infarcted area of animals treated with hADMSCs + P5 than that in hADMSC-treated or control animals, concomitant with reduced number of phagocytic, annexin3-positive cells in the peri-infarcted region. However, the combination therapy did not increase the vascular density in the peri-infarcted area after stroke. In conclusion, administration of hADMSC-loaded p5 peptide to post-stroke rats created conditions that supported survival of drug-loaded hADMSCs after cerebral ischemia, suggesting its therapeutic potential in patients with stroke.
Original languageEnglish
Number of pages11
JournalTranslational Stroke Research
Early online date6 May 2020
DOIs
Publication statusE-pub ahead of print - 6 May 2020
Externally publishedYes

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    Paudyal, A., Ghinea, F. S., Driga, M. P., Fang, W., Alessandri, G., Combes, L., Degens, H., Slevin, M., Hermann, D. M., & Popa-wagner, A. (2020). p5 Peptide-Loaded Human Adipose-Derived Mesenchymal Stem Cells Promote Neurological Recovery After Focal Cerebral Ischemia in a Rat Model. Translational Stroke Research. https://doi.org/10.1007/s12975-020-00805-0