Canine mesenchymal stem cells are neurotrophic and angiogenic: An in vitro assessment of their paracrine activity. (November 2016)

• Record Type: Journal Article
• Authors: Al Delfi, I.R.; Sheard, J.J.; Wood, C.R.; Vernallis, A.; Innes, J.F.; Myint, P.; Johnson, W.E.B.
• Is Part Of: Veterinary journal. Volume 217(2016)
• Page Start: 10
• Page End: 17
• Publication Date: 2016-11
• Subjects: Angiogenesis -- Central nervous system repair -- Mesenchymal stem/stromal cell -- Nerve growth -- Secretome; Veterinary medicine -- Periodicals; 636
• DOI: 10.1016/j.tvjl.2016.09.003
• Languages: English
• ISSNs: 1090-0233

Abstract

Highlights: Mesenchymal stem cells (MSCs) can be isolated and cultured from adipose tissue biopsies from dogs. Canine MSCs secrete factors to stimulate neuronal outgrowth and endothelial proliferation, migration and tubule formation. Canine MSCs and secretomes may promote wound repair following transplants in dogs with natural spinal cord injury. Abstract: Mesenchymal stem cells (MSCs) have been used in cell replacement therapies for connective tissue damage, but also can stimulate wound healing through paracrine activity. In order to further understand the potential use of MSCs to treat dogs with neurological disorders, this study examined the paracrine action of adipose-derived canine MSCs on neuronal and endothelial cell models. The culture-expanded MSCs exhibited a MSC phenotype according to plastic adherence, cell morphology, CD profiling and differentiation potential along mesenchymal lineages. Treating the SH-SY5Y neuronal cell line with serum-free MSC culture-conditioned medium (MSC CM) significantly increased SH-SY5Y cell proliferation ( P < 0.01), neurite outgrowth ( P = 0.0055) and immunopositivity for the neuronal marker βIII-tubulin ( P = 0.0002). Treatment of the EA.hy926 endothelial cell line with MSC CM significantly increased the rate of wound closure in endothelial cell scratch wound assays ( P = 0.0409), which was associated with significantly increased endothelial cell proliferation ( P < 0.05) and migration ( P = 0.0001). Furthermore, canine MSC CM induced endothelial tubule formation in EA.hy926 cells in a soluble basement membrane matrix. Hence, this study has demonstrated that adipose-derived canine MSC CM stimulated neuronal and endothelial cells probably through the paracrine activity of MSC-secreted factors. This supports the use of canine MSC transplants or their secreted products in the clinical treatment of dogs with neurological disorders and provides some insight into possible mechanisms of action.