PS196. Increased Adipose-Derived Mesenchymal Stem Cells Counts and Pro-B-Type Natriuretic Peptide in Patients With Critical Limb Ischemia

Abstract

Mesenchymal stem cells (MSCs) have been shown to improve regeneration of injured tissues in vivo. Several in vitro studies and animal models have demonstrated improvement in MSCs paracrine effects under hypoxic conditions. Moreover, several studies suggested that the pro B-type natriuretic peptide (pro-BNP) could be involved in the stimulation of postischemic vascular regeneration. The purpose of this study was to investigate the effect of critical limb ischemia, in a human model, on in situ adipose-derived mesenchymal stem cells (ADMSCs) and to determine whether serum levels of N-terminal pro-BNP correlate with ADMSCs counts and associated paracrine effects. Lipoaspirate samples of ≥10 mL were collected from ischemic limbs (ischemic group) and compared with control samples (without ischemia). MSCs were characterized by frequency, viability, differentiation potential, cytokines expression, and cell surface markers. Serum NT pro-BNP was measured as well. MSCs counts were ninefold to 10-fold higher in patients with ischemic limbs (mean 7952 ± 542 MSC/mL) than controls (mean 790 ± 65 MSC/mL). Pro-BNP levels (range, 1878-4757 pg/mL) were approximately eightfold to 26-fold higher than in age- and sex-matched controls. Furthermore, there were positive correlations between pro-BNP levels and MSCs counts in the ischemic group. Patients with critical limb ischemia (CLI) have higher levels of pro-BNP and MSCs counts than controls. Increased levels of pro-BNP and MSCs counts can be considered humoral and cellular surrogates of ischemia and hypoxia in patients with CLI. This supports recent studies that suggest that the increase production of peripheral BNP may be a stem cells-mediated response to stimulate angiogenesis in the ischemic skeletal muscles.