Comparison of proliferative and immunomodulatory potential of adipose-derived mesenchymal stem cells from young and geriatric cats

Abstract

Objectives The objective of this study was to compare the ability of adipose-derived mesenchymal stem cells (aMSCs) generated from young vs geriatric cats to proliferate in culture, suppress lymphocyte proliferation and undergo senescence. Methods Adipose tissues from five young (<5 years) and six geriatric (>10 years) cats were harvested and cryopreserved for subsequent aMSC isolation and culture. aMSC proliferation in culture was compared via determination of time until passage two and by 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory capacity of aMSCs was assessed using lymphocyte proliferation assays, and senescence was evaluated using senescence-associated B-galactosidase (SABG) expression. All assays were performed on aMSCs between passage two and passage three. Results aMSCs from geriatric cats took significantly longer ( P = 0.008) to reach passage two (median 11 days, range 9-22 days) compared with aMSCs from young healthy cats (median 7 days, range 6-8 days). No significant difference was detected between young and geriatric cats in terms of their ability to suppress lymphocyte proliferation. SABG expression was not significantly different between young and geriatric aMSCs. Conclusions and relevance Compared with young feline aMSCs, geriatric aMSCs are significantly impaired in their ability to rapidly proliferate to passage two following initial culture, presenting a concern for autologous therapy. Nonetheless, once the cells are expanded, young and geriatric cat aMSCs appear to be equivalent in terms of their ability to functionally suppress T-cell activation and proliferation.

Adipose‐derived autologous mesenchymal stem cell transfusion for the treatment of feline chronic gingivostomatitis in a domestic shorthair cat

“…aMSCs from geriatric cats have impaired growth compared with those harvested from young cats, for example. 20 The use of allogenic MSCs would have negated this problem and is an attractive alternative with regards to convenience. Indeed, the use of allogenic MSCs for the treatment of cats with FCGS has been shown to be successful.…”

Substantial Overview on Mesenchymal Stem Cell Biological and Physical Properties as an Opportunity in Translational Medicine

“…Albeit the isolation and the characterization of feline BM-derived MSC started in 2002 [40], several studies evidenced the possibility to isolate MSC from other tissue sources in order to test these cells for treating a range of disorders. Interesting data show that feline Ad-MSC isolated from a young subject are more proliferative in the initial phase of culture than those obtained by a geriatric cat [41]. Differently, when cells are expanded, both cell types were equivalent in respect to their ability to functionally suppress T-cell activation and proliferation [41].…”

“…Interesting data show that feline Ad-MSC isolated from a young subject are more proliferative in the initial phase of culture than those obtained by a geriatric cat [41]. Differently, when cells are expanded, both cell types were equivalent in respect to their ability to functionally suppress T-cell activation and proliferation [41]. However, it was demonstrated that excess passaging influences some biological cell properties, decreasing both cell proliferation and expression of hematopoietic marker CD45 [42].…”

Mesenchymal stem cell therapy in cats: Current knowledge and future potential

“…Numerous groups have demonstrated that feline MSCs inhibit activated T lymphocyte proliferation. 6,7,18,19 Feline MSCs also reduce neutrophil production of reactive oxygen species. 20 The interaction of feline MSCs with other cells of the innate and humoral immune systems, including dendritic cells, monocytes, eosinophils, NK cells and B lymphocytes, and the mechanisms involved have not yet been detailed but will be important areas for future studies.…”

“…However, these data represent relatively low numbers of cats (seven cats for each group) and no attempts were made to optimize allogeneic cell efficacy (ie, increasing cell dose or number of doses). As described for most species, MSC numbers may decline with age, leading to an increased lag time to culture expand these cells for therapeutic purposes in geriatric cats 19. Concurrent disease states, such as uremia, may have an effect on the therapeutic capability of autologous MSCs, as previous studies have demonstrated that MSCs obtained from uremic rats exhibit reduced proliferation in culture, premature senescence and decreased capacity to induce angiogenesis 36,37.…”