Evaluation of canine adipose-derived mesenchymal stem cells for neurological functional recovery in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common condition in veterinary medicine that is difficult to manage.Veterinary regenerative therapy based on adipose mesenchymal stem cells seem to be an effective strategy for the treatment of traumatic brain injury. In this study, we evaluated therapeutic efficacy of canine Adipose-derived mesenchymal stem cells (AD-MSCs)in a rat TBI model, in terms of improved nerve function and anti-neuroinflammation. RESULTS: Canine AD-MSCs promoted neural functional recovery, reduced neuronal apoptosis, and inhibited the activation of microglia and astrocytes in TBI rats. According to the results in vivo, we further investigated the regulatory mechanism of AD-MSCs on activated microglia by co-culture in vitro. Finally, we found that canine AD-MSCs promoted their polarization to the M2 phenotype, and inhibited their polarization to the M1 phenotype. What's more, AD-MSCs could reduce the migration, proliferation and Inflammatory cytokines of activated microglia, which is able to inhibit inflammation in the central system. CONCLUSIONS: Collectively, the present study demonstrates that transplantation of canine AD-MSCs can promote functional recovery in TBI rats via inhibition of neuronal apoptosis, glial cell activation and central system inflammation, thus providing a theoretical basis for canine AD-MSCs therapy for TBI in veterinary clinic.

Biological characteristics of canine adipose-derived mesenchymal stem cells cultured in hypoxia / 中国组织工程研究

BACKGROUND: Previous studies have found that hypoxia has different effects on the proliferation and differentiation of mesenchymal stem cells and secretion of cytokines, but the effect of hypoxia on canine adipose-derived mesenchymal stem cells has not been seen. OBJECTIVE: To investigate the effect of hypoxic environment on the biological characteristics of canine adipose-derived mesenchymal stem cells. METHODS: Canine adipose-derived mesenchymal stem cells were isolated and cultured by enzyme digestion. Passage 2 adipose-derived mesenchymal stem cells could be divided into normoxia group (21% oxygen volume fraction) and hypoxia group (5% oxygen volume fraction). Morphological characteristics, proliferation speed, cell surface marker expression, differentiation capacity, and cytokine secretion level were compared between the two groups. RESULTS AND CONCLUSION: (1) The growth of adipose-derived mesenchymal stem cells cultured in hypoxic environment was good. The cell morphology was fusiform and polyhedral, the same as that of the normoxia group. (2) The proliferation rate of cells in the hypoxia group was accelerated, and the cell doubling time was shorter than that in the normoxia group (all P < 0.05). The differentiation time of lipogenesis and osteogenesis was shortened. (3) The expression of CD90, CD44 and CD105 was high in both normoxia group and hypoxia group, while the expression of CD45 was low. (4) The mRNA expression levels of brain-derived neurotrophic factor and vascular endothelial growth factor in the hypoxia group were 2.3 times (P < 0.05) and 3.0 times (P < 0.05) higher than those in the normoxia group. (5) The results indicated that the hypoxic environment had no significant effect on the morphology and surface marker of adipose-derived mesenchymal stem cells, but promoted cell proliferation, differentiation and cytokine secretion.