Platelets in Wound Healing: What Happens in Space?

Abstract

Beyond their fundamental role in hemostasis, platelets importantly contribute to other processes aimed at maintaining homeostasis. Indeed, platelets are a natural source of growth factors and also release many other substances-such as fibronectin, vitronectin, sphingosine 1-phosphate-that are important in maintaining healthy tissues, and ensuring regeneration and repair. Despite rare thrombotic events have been documented in astronauts, some in vivo and in vitro studies demonstrate that microgravity affects platelet's number and function, thus increasing the risk of hemorrhages and contributing to retard wound healing. Here we provide an overview about events linking platelets to the impairment of wound healing in space, also considering, besides weightlessness, exposure to radiation and psychological stress. In the end we discuss the possibility of utilizing platelet rich plasma as a tool to treat skin injuries eventually occurring during space missions.

Keywords: microgravity; platelet rich plasma; platelets; regeneration; wound healing.

FIGURE 1

The role of platelets in the different sequential steps of wound healing. In wound healing, four steps are recognized, i.e., hemostasis, inflammation, proliferation, and remodeling/maturation. From the beginning of the process platelets play a fundamental role, starting from the aggregation and formation of a clot to stop bleeding (hemostasis). They also contribute to the recruitment of immune cells (inflammatory phase), to the formation of granulation tissue (proliferative phase), to the remodeling and contraction of the wound to reconstitute structural continuity and, possibly, function. vWF, von Willebrand factor; FGF, Fibroblast Growth Factor; VEGF, Vascular Endothelial Growth Factor; HGF, Hepatocyte Growth Factor; PDGF, Platelet-Derived Growth Factor; TGF-β, Transforming Growth Factor β; MMPs, Matrix Metallo-Proteinases.

FIGURE 2

The role of microgravity in inducing hemorrhagic or thrombotic events. Microgravity induces hemorrhagic events by decreasing platelet number and impairing platelet functions. On the other hand, microgravity induces blood stasis in the upper body, vascular endothelial dysfunction and alterations in blood volume and blood viscosity, all events which might contribute to the increase of thrombotic incidents.

FIGURE 3

Microgravity effects on platelets and the downstream effects on wound healing. Microgravity induces thrombocytopenia and decreases the activation of platelets, two phenomena which concur to delay tissue repair in space. The decreased production/release of different growth factors (EGF, PDGF, FGF and TGF-β) has downstream effects on other important players of the different steps of wound healing. EGF, Epidermal Growth Factor; PDGF, Platelet-Derived Growth Factor; FGF, Fibroblast Growth Factor; TGF-β, Transforming Growth Factor β.

FIGURE 4

Platelet Rich Plasma (PRP) preparation and efficacy in different clinical conditions. PRP is prepared by centrifugation of peripheral blood to concentrate platelets. Platelet derivatives are promising tools to promote regeneration and healing for future space travel. Indeed, they have yielded excellent results in different medical fields, from oral and maxillofacial surgical procedures, to the treatment of symptomatic osteoarthritis patients and diabetic ulcers. NFκB, Nuclear Factor kappa B; TGF-β, Transforming Growth Factor β MMPs, Matrix Metallo-Proteinases, 5-HT, serotonin.