Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells

Abstract

Neuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool. So far, the presence of NPY in PL and its biological effects on the adipose stromal cell fraction (ASCs) have never been investigated. Here, we aimed to identify endogenous sources of NPY such as PL-based preparations and to investigate which biological properties PL-derived NPY is able to exert on ASCs. The results show that PL contains a high amount of NPY, which is in part also excreted by ASCs when stimulated with PL. The protein levels of the three main NPY subtype receptors (Y1, Y2, Y5) are unaltered by stimulation of ASCs with PL, but their inhibition through selective pharmacological antagonists, considerably enhances migration, and a parallel reduction of angiogenic features of ASCs including decrease in VEGF mRNA and intracellular calcium levels, both downstream targets of NPY. The expression of VEGF and NPY is enhanced within the sites of neovascularisation of difficult wounds in patients after treatment with leuco-platelet concentrates. Our data highlight the presence of NPY in PL preparations and its peripheral effects on adipose progenitors.

The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

“…The loop number and network length found in Matrigel assays of ASCs co-cultured with platelet lysate are notably attenuated in parallel with decreased VEGF expression in the presence of a specific NPY receptor antagonist. Taken together, platelet NPY plays a vital role as a VEGF mediator in ASC angiogenesis [56]. Another type of cell-affecting endothelial homeostasis and function is fibroblasts.…”

Oral Plaque from Type 2 Diabetic Patients Reduces the Clonogenic Capacity of Dental Pulp-Derived Mesenchymal Stem Cells

“…The clinical features of all patients are reported in Table 1. Subcutaneous adipose stromal cells (ASCs, primary cell lines 55P and 56P) were isolated as previously described [11, 27], according to the approved protocol (Ethical Committee of “Sant'Andrea” Hospital in Rome, Ref. 49_2013/28.01.2016).…”

Autonomic nerve dysfunction and impaired diabetic wound healing: The role of neuropeptides

“…Specifically, NPY modulates cell migration, cytokine release from macrophages and helper T cells, antigen presentation as well as activation of natural killer cells and antibody production (Wheway et al, 2007;Groneberg et al, 2004;Bedoui et al, 2003). Platelet lysate derived NPY was recently shown to affect migration and angiogenesis potential of human adipose derived stromal cells and co-localized with endothelial markers CD31 and VEGF in difficult to heal wound samples treated with lysate (Businaro et al, 2018). NPY is mostly known to be associated with tendon and cartilage healing, but through its pro-angiogenic receptors NPY-2R and NPY-5R it also influences cutaneous healing (Zukowska et al, 2003a;Salo et al, 2008;Salo et al, 2007;Ackermann et al, 2002).…”