Optimising platelet secretomes to deliver robust tissue‐specific regeneration

Abstract

Promoting cell proliferation is the cornerstone of most tissue regeneration therapies.As platelet-based applications promote cell division and can be customised for tissuespecific efficacy, this makes them strong candidates for developing novel regenerative therapies. Therefore, the aim of this study was to determine if platelet releasate could be optimised to promote cellular proliferation and differentiation of specific tissues. Growth factors in platelet releasate were profiled for physiological and supraphysiological platelet concentrations. We analysed the effect of physiological and supraphysiological releasate on C2C12 skeletal myoblasts, H9C2 rat cardiomyocytes, human dermal fibroblasts (HDF), HaCaT keratinocytes, and chondrocytes. Cellular proliferation and differentiation were assessed through proliferation assays, mRNA, and protein expression. We show that supraphysiological releasate is not simply a concentrated version of physiological releasate. Physiological releasate promoted C2C12, HDF, and chondrocyte proliferation with no effect on H9C2 or HaCaT cells. Supraphysiological releasate induced stronger proliferation in C2C12 and HDF cells compared with physiological releasate. Importantly, supraphysiological releasate induced proliferation of H9C2 cells. The proliferative effects of skeletal and cardiac muscle cells were in part driven by vascular endothelial growth factor alpha. Furthermore, supraphysiological releasate induced differentiation of H9C2 and C2C12, HDF, and keratinocytes. This study provides insights into the ability of releasate to promote muscle, heart, skin, and cartilage cell proliferation and differentiation and highlights the importance of optimising releasate composition for tissue-specific regeneration.

Wound healing: cellular mechanisms and pathological outcomes

“…Platelets are crucial in the recruitment of immune cells to the injury site, by either directly capturing immune cells in the eschar, or by releasing a secretome of chemokine attractants upon degranulation [6]. In fact, the platelet secretome also contains growth factors that stimulate resident skin cells, including fibroblasts and keratinocytes [9]. As the most abundant cell type during early repair, platelets play an active role in the early inhibition of bacterial infection.…”

Intraovarian injection of platelet-rich plasma in assisted reproduction: too much too soon?

“…In recent years, there has been significant interest in exploiting PRP in regenerative medicine. Particular attention has been paid to musculoskeletal ( Scully et al , 2019 , 2020 ), oral-maxillofacial ( Xu et al , 2020 ) and osteoarthritis ( Evans et al , 2020 ) applications to name but a few. For a more comprehensive account, the reader is referred to a review ( Scully et al , 2018 ).…”

Platelet releasate normalises the compromised muscle regeneration in a mouse model of hyperlipidaemia

“…Platelet releasate is rich in numerous growth factors, cytokines and myokines, constituting a powerful biomaterial for regenerative medicine (Sassoli et al., 2018; Scully et al., 2018a, b, 2020; Scully & Matsakas, 2019; Tsai et al., 2018). Given that, platelet releasate increases the myogenic potential and promotes differentiation of myoblasts in vitro and ex vivo (Scully et al., 2018a, 2020), we sought to determine whether platelet releasate mitigates the impaired skeletal muscle regeneration of the ApoE –/– mice in vivo . We report here for the first time, that treatment with platelet releasate normalised regeneration of ApoE –/– skeletal muscle to the levels of wild‐type as judged by increased CSA of regenerating fibres (i.e.…”