Age, atherosclerosis and type 2 diabetes reduce human mesenchymal stromal cell-mediated T-cell suppression

Abstract

To this end human MSCs were isolated from adipose tissue and the MSC:CD4(+) T-cell suppression was assessed in a co-culture system. In summary, this study demonstrates that advanced age, atherosclerosis and type 2 diabetes mellitus reduce the functional potency of MSCs. Optimizing the criteria for the selection of MSC donors could enhance the results of cell-based therapies.

Fig. 1

Age-associated decline in mesenchymal stromal cell (MSC)-mediated CD4⁺ T-cell suppression capacity. a MSCs from elderly donors (E-MSCs, ≥65 years, n = 23) are less efficient than those of non-elderly adults (A-MSCs, <65 years, n = 27) to suppress CD4⁺ T-cell proliferation at 1:8 MSC:CD4⁺ T cell ratio (**p = 0.003). b The suppressive effect of MSCs on CD4⁺ T cells depends on the MSC:CD4⁺ T-cell ratio (**p = 0.004). Twice the number of E-MSCs are required to affect CD4⁺ T-cell suppression to the same extent as A-MSCs (p > 0.9). c The effect of MSC donor age on the decline of CD4⁺ T-cell suppression is observed in patients with atherosclerosis (ATH; n = 18; p = 0.02, r = 0.4) and without ATH (non-ATH; n = 9; p = 0.02, r = 0.7)

Fig. 2

Reduced MSC-mediated T-cell suppression capacity in patients with atherosclerosis and type 2 diabetes. a MSCs from patients with atherosclerosis (ATH; n = 18; *p = 0.02) have a decreased capacity to suppress CD4⁺ T-cell proliferation at 1:8 MSC:CD4⁺ T cell ratio compared to age-matched controls without atherosclerosis (non-ATH, n = 9). b MSCs from patients with ATH (n = 12) and type 2 diabetes mellitus (T2DM) (n = 12) have impaired suppressive capacity compared to age-matched ATH controls (*p = 0.04). c MSC function is compromised in age-matched patients with chronic inflammatory diseases (non-ATH < ATH < ATH+T2DM; n = 7 per group; *p = 0.02, **p = 0.002)