Influence of Donor's Age on Immunomodulatory Properties of Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Abstract

Osteoarthritis challenges traditional therapies and remains a leading cause of lameness in older dogs. Regenerative medicine offers new strategies, typically involving the injection of autologous adipose-derived mesenchymal stem cells (MSCs). Conversely, allogenic MSCs are appealing candidates to palliate patient morbidity and cell preparation time. Regardless of the source of cells, identifying critical donor characteristics, such as age, is essential to obtain the most competent MSCs. The objectives of this study were to determine the influence of donor's age on proliferation, gene expression, and immunomodulatory properties of MSCs in dogs. Canine adipose tissue-derived MSCs (cAD-MSCs) were isolated from the falciform-ligament adipose tissues of nine pairs of gender-matched young (<2 years) or old (>7 years) client-owned dogs undergoing abdominal surgery. Growth kinetics, transcriptome before and after stimulation by tumor necrosis factor alpha and interferon gamma, MSC-induced lymphocyte suppression assay, and secretion of prostaglandin E2 (PGE2) and indoleamine 2,3-dioxygenase (IDO) were compared between cells obtained from young or old dogs. The doubling times at passages 2 and 3 were shorter when MSCs were isolated from young (34.8 ± 1.8 h and 46.3 ± 2.3 h) rather than old dogs (56.5 ± 8.0 h and 123.8 ± 46.7 h, P < 0.05). The MSC transcriptomes from both populations were similar without stimulation, while stimulation resulted in a 3-fold greater expression of osteogenic gene, fibroblast growth factor 10, in cells from old dogs. cAD-MSCs from young dogs suppressed proliferation of activated T cells more strongly (P < 0.05), although secretion of PGE2 and IDO did not differ between groups. In conclusion, donors' age affected proliferation, immunomodulatory properties of cAD-MSCs, and increased expression of osteogenic gene under proinflammatory conditions in our population of dogs. Collectively, our results provide evidence to support further evaluation of allogenic MSC therapies derived from young donors as alternatives to autologous MSC therapy in older dogs.