Abstract
Blood-derived factor preparations are being clinically employed as tools for promoting tissue repair and regeneration. Here we set out to characterize the in vitro angiogenic potential of two types of frequently used autologous blood-derived secretomes: platelet-rich plasma (PRP) and hypoxia preconditioned plasma (HPP)/serum (HPS). The concentration of key pro-angiogenic (VEGF) and anti-angiogenic (TSP-1, PF-4) protein factors in these secretomes was analyzed via ELISA, while their ability to induce microvessel formation and sprouting was examined in endothelial cell and aortic ring cultures, respectively. We found higher concentrations of VEGF in PRP and HPP/HPS compared to normal plasma and serum. This correlated with improved induction of microvessel formation by PRP and HPP/HPS. HPP had a significantly lower TSP-1 and PF-4 concentration than PRP and HPS. PRP and HPP/HPS appeared to induce similar levels of microvessel sprouting; however, the length of these sprouts was greater in HPP/HPS than in PRP cultures. A bell-shaped angiogenic response profile was observed with increasing HPP/HPS dilutions, with peak values significantly exceeding the PRP response. Our findings demonstrate that optimization of peripheral blood cell-derived angiogenic factor signalling through hypoxic preconditioning offers an improved alternative to simple platelet concentration and release of growth factors pre-stored in platelets.
Highlights
Over the past decade, there has been a growing interest in the therapeutic application of autologous blood-derived products for the treatment of various skin pathologies and chronic wounds [1,2,3,4,5].Under physiological conditions, a wound can rapidly regenerate through a series of well-defined wound healing stages, namely haemostasis, inflammation, proliferation and angiogenesis, and Biomedicines 2020, 8, 16; doi:10.3390/biomedicines8010016 www.mdpi.com/journal/biomedicinesBiomedicines 2020, 8, 16 eventually tissue remodelling [6,7]
To establish a growth factor concentration baseline, we first quantitatively analyzed via ELISA the concentration of key angiogenesis-related protein factors (VEGF, TSP-1, PF-4) in normal plasma and serum, before proceeding to test their concentration in platelet-rich plasma (PRP) and hypoxia preconditioned plasma (HPP)/Hypoxia Preconditioned Serum (HPS)
Due to a large standard deviation in factor levels, no statistically significant differences could be observed between the three tested secretomes, except for HPP prepared with EDTA as anticoagulant, which had a significantly lower VEGF concentration (p < 0.001)
Summary
There has been a growing interest in the therapeutic application of autologous blood-derived products for the treatment of various skin pathologies and chronic wounds [1,2,3,4,5].Under physiological conditions, a wound can rapidly regenerate through a series of well-defined wound healing stages, namely haemostasis, inflammation, proliferation and angiogenesis, and Biomedicines 2020, 8, 16; doi:10.3390/biomedicines8010016 www.mdpi.com/journal/biomedicinesBiomedicines 2020, 8, 16 eventually tissue remodelling [6,7]. The efficiency and reliability of this complex system of cellular responses, which are powered by a myriad of molecular cascades, suggests that targeted reproduction of the basic foundation underlying the natural process would provide a useful tool for promoting tissue repair and regeneration on-demand. These treatments could be readily applied in the clinical setting, despite an incomplete understanding of the precise set of rules that govern such mechanisms, at present. The main purpose of the application of blood-derived secretomes in wounded or ischaemic tissues is the targeted stimulation and support of the cellular responses that naturally drive angiogenesis and tissue repair, via protein growth factor signalling
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