Cellular hypoxic preconditioning is being employed to obtain complex, yet physiological, secretomes rich is angiogenic factors. We previously proposed exposing peripheral blood cells (PBCs) to hypoxic stress stimulation, and demonstrated that controlled release of PBC-derived factor mixtures induces directional microvessel growth in vitro. Hypoxia therefore provides a useful tool for enhancing the angiogenic potential of blood plasma, by generating compositions based on PBCs' natural responses to a wound-like microenvironment. Here, we discuss various methods for preparing and delivering Hypoxia Preconditioned Plasma (HPP), i.e., plasma derived after extracorporeal conditioning of anticoagulated blood under physiological temperature and hypoxia. Special emphasis is given to those approaches that will likely facilitate the clinical translation of HPP-based therapies. We finally draw a comparison between HPP and other, currently available blood-based products, and present the case that its arrival paves the way for developing next-generation autologous therapies toward angiogenesis-supported tissue repair and regeneration.
Keywords: angiogenesis; blood; factors; hypoxia; ischaemia; plasma; preconditioning; regeneration; therapy; wound.