Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery

Abstract

Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell–cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies.

RETRACTED: Extracellular Vesicles Embedded with Persistent Luminescence Nanoparticles Exhibiting Near-Infrared Emission for Long-Term Tracking in Primary Tumors

“…5 They are secreted by most cell types and play a role in intercellular communication systems, facilitating the local as well as systemic transport of RNA and proteins. 6 These vesicles can be extracted from various body fluids as well as cell culture medium. The small size and bubble-like shape of EVs allows their free movement from one cell to another, the release of their contents through the cell membrane, and their merging with other EVs.…”

Beyond Basic Characterization and Omics: Immunomodulatory Roles of Platelet-Derived Extracellular Vesicles Unveiled by Functional Testing

“…Platelets represent an excellent cell model for studying the impact of different signaling pathways on the PEVome. Therefore, exploration of the tunability of the PEVome in the context of the immune system is relevant for e.g., the possibility to tune the PEVs towards a defined profile, which would be of interest for the development of drug delivery systems or advanced molecular therapeutic products (AMTP) with innate therapeutic capacity 83 . Also, the high interest in the diagnostic biomarker use of PEVs still demands a better understanding of the variability of the PEVome and its relation to the PEV-inducing signal, whether it is e.g., viral by CLEC-2 84 , thrombotic, mediated by thrombin and collagen receptors 85 , or singularly by GPVI.…”

Proteomics of human platelet lysates and insight from animal studies on platelet protein diffusion to hippocampus upon intranasal administration

“… 1,2 HPLs are increasingly sourced from clinical-grade allogeneic platelet concentrates (PCs) produced by licensed blood establishments. 3 Over time, HPLs have been recognized as invaluable cell culture supplements in the cell therapy industry for xeno-free propagation of therapeutic mesenchymal stromal cells (MSCs), differentiated cells, like chondrocytes, and immune cells, including CAR-T cells. 4–6 In addition, HPLs are progressively adopted across a spectrum of regenerative medicine applications, 3 such as for treating osteoarthritis 7,8 and musculoskeletal injuries, 9 stimulating bone regeneration, 10 releasing dry eye syndrome, 11,12 and curing diabetic ulcers.…”

“… 3 Over time, HPLs have been recognized as invaluable cell culture supplements in the cell therapy industry for xeno-free propagation of therapeutic mesenchymal stromal cells (MSCs), differentiated cells, like chondrocytes, and immune cells, including CAR-T cells. 4–6 In addition, HPLs are progressively adopted across a spectrum of regenerative medicine applications, 3 such as for treating osteoarthritis 7,8 and musculoskeletal injuries, 9 stimulating bone regeneration, 10 releasing dry eye syndrome, 11,12 and curing diabetic ulcers. 13 Additionally, tailor-made HPLs, enriched in neurotrophic factors, neurotransmitters, antioxidants, and protease inhibitors, are showing promise in preclinical studies as a pleiotropic biotherapy of complex neurological disorders like Parkinson's disease, 14,15 Alzheimer's disease, 16 amyotrophic lateral sclerosis, 17 traumatic brain injury, 18,19 and stroke, 20 as reviewed recently.…”

“…This is further justified as there exist variables in HPL preparation, encompassing individual blood donor variability, methods of PC collection, pooling, and platelet lysis, degranulation, and further processing. 3,22,23 Such manufacturing differences are thought to yield HPLs with distinct protein profiles, potentially altering their effectiveness in cell expansion and tissue regeneration and protection, as observed when using autologous platelet rich plasma. 24,25 For instance, HPLs can be prepared through direct freeze-thawing of PCs suspended in plasma or from isolated platelets.…”