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

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 periinfarcted 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.

Efficacy of Human Adipose Derived Mesenchymal Stem Cells in Promoting Skin Wound Healing

“…They are isolated from adipose tissue around blood vessels and cultured. They can differentiate into a variety of cells, including bone cells, chondrocytes, and nerve cells [ 18 ]. Compared with other MSCs, ADMSCs are not only easy to obtain but also show multidirectional differentiation potential, and there is no ethical dispute [ 19 ].…”

Mesenchymal Stem Cells: Therapeutic Mechanisms for Stroke

“…For instance, MSC therapy combined with royal jelly significantly reduced the infarcted volumes, cerebral edema, and serum pro-inflammatory cytokine levels [ 73 ]. The administration of hADSC-loaded P5 peptide to post-stroke rats created conditions that supported drug-loaded hADSC survival, and hADSC loaded with p5 peptide reduced the number of inflammatory cells around the lesion, but did not increase the vascular density around the infarction area [ 74 ]. Gene-modified MSCs can express biologically active gene products, and, therefore, serve as effective vectors for therapeutic gene transfer to the brain.…”

Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis

“…One important finding of the study is the interest in using EVs from IFNγ pre-activated MSCs to enhance their beneficial effect in the lungs of SSc mice. It has already been shown that MSC priming by hypoxia or genetic modification may enhance their therapeutic properties in other applications [19,20]. Improvement of fibrotic, remodeling and inflammatory markers was observed by comparison with EVs from non-activated MSCs.…”