Skin-derived precursors from human subjects with Type 2 diabetes yield dysfunctional vascular smooth muscle cells

Objective : Few methods enable molecular and cellular studies of vascular aging or Type 2 diabetes (T2D). Here, we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and results : Skin-derived precursors (SKPs) were cultured from biopsies ( N =164, ∼1 cm 2 ) taken from the edges of surgical incisions of older adults ( N =158; males 72%; mean age 62.7 ± 13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield). The number of SKPs isolated from subjects with T2D was ∼50% lower than those without T2D (cells/g: 0.18 ± 0.03, N =58 versus 0.40 ± 0.05, N =100, P 2+ concentrations (AU: 1,968 ± 160, N =7 versus 1,386 ± 170, N =13, P 2+ cycling responses to norepinephrine (NE) (AUC: 177,207 ± 24,669, N =7 versus 101,537 ± 15,881, N =20, P 2+ cycling (events s −1 cell −1 : 0.011 ± 0.004, N =8 versus 0.021 ± 0.003, N =19, P 50 nM: 72.3 ± 63.6, N =5 versus 3,684 ± 3,122, N =9, P in vitro (% closure: 21.9 ± 3.6, N =4 versus 67.0 ± 10.3, N =4, P