Can the administration of platelet lysates to the brain help treat neurological disorders?

Abstract

Neurodegenerative disorders of the central nervous system (CNS) and brain traumatic insults are characterized by complex overlapping pathophysiological alterations encompassing neuroinflammation, alterations of synaptic functions, oxidative stress, and progressive neurodegeneration that eventually lead to irreversible motor and cognitive dysfunctions. A single pharmacological approach is unlikely to provide a complementary set of molecular therapeutic actions suitable to resolve these complex pathologies. Recent preclinical data are providing evidence-based scientific rationales to support biotherapies based on administering neurotrophic factors and extracellular vesicles present in the lysates of human platelets collected from healthy donors to the brain. Here, we present the most recent findings on the composition of the platelet proteome that can activate complementary signaling pathways in vivo to trigger neuroprotection, synapse protection, anti-inflammation, antioxidation, and neurorestoration. We also report experimental data where the administration of human platelet lysates (HPL) was safe and resulted in beneficial neuroprotective effects in established rodent models of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, and stroke. Platelet-based biotherapies, prepared from collected platelet concentrates (PC), are emerging as a novel pragmatic and accessible translational therapeutic strategy for treating neurological diseases. Based on this assumption, we further elaborated on various clinical, manufacturing, and regulatory issues that need to be addressed to ensure the ethical supply, quality, and safety of HPL preparations for treating neurodegenerative and traumatic pathologies of the CNS. HPL made from PC may become a unique approach for scientifically based treatments of neurological disorders readily accessible in low-, middle-, and high-income countries.

Keywords: Brain; Extracellular vesicles; Growth factors; Neuroprotection; Neurorestoration; Platelet neurotrophins.

Fig. 1

Human platelet lysate preparation methods. They are either generated from fresh or expired platelet concentrates collected by apheresis or obtained from whole blood donations. Fresh or expired platelet concentrates can be lysed by several freeze/thaw steps, by platelet activation induced by addition of thrombin or calcium chloride (CaCl2), by sonication or by solvent/detergent (S/D) treatment. In all these methods, the cells debris are depleted by centrifugation and discarded after cells lysis and the supernatant recovered and aliquoted. HPL human platelet lysate, PBS phosphate buffer saline, PC platelet concentrates

Fig. 2

Summary of the neuroprotective and neurorestorative activities of human platelet lysate reported in animal models of neurodegenerative diseases and CNS injuries. HPL are produced from platelets. In the animal models of Alzheimer and Parkinson’s diseases, amyotrophic lateral sclerosis, stroke, and traumatic brain injury human platelet lysates are delivered either by intranasal, intracerebroventricular administration, or by topical deposition at the desired region. The main effect of the HPL is their ability to stimulate neurogenesis and their neuroprotective activity. HPL human platelet lysate, NSC neural stem cell, ROS reactive oxygen species