Canine mesenchymal stem cells are neurotrophic and angiogenic: An in vitro assessment of their paracrine activity.
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.
Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
I R
IR
Al Delfi
Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
J J
JJ
Sheard
Department of Biological Sciences, Faculty of Medicine, Dentistry and Life Sciences, University of Chester, Parkgate Road, Chester, Cheshire CH1 4BJ, UK.
C R
CR
Wood
Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
A
A
Vernallis
Veterinary Tissue Bank Ltd, Brynkinalt Business Centre, Wrexham LL14 5NS, UK.
J F
JF
Innes
Veterinary Tissue Bank Ltd, Brynkinalt Business Centre, Wrexham LL14 5NS, UK.
P
P
Myint
Department of Biological Sciences, Faculty of Medicine, Dentistry and Life Sciences, University of Chester, Parkgate Road, Chester, Cheshire CH1 4BJ, UK. Electronic address: eustace.johnson@chester.ac.uk.
W E B
WE
Johnson
D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D004285:Dogs / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019899:Paracrine Communication; D014945:Wound Healing
D017077:Culture Media, Conditioned
Angiogenesis; Central nervous system repair; Mesenchymal stem/stromal cell; Nerve growth; Secretome