Promoting cell proliferation is the cornerstone of most tissue regeneration therapies. As platelet-based applications promote cell division and can be customised for tissue-specific 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.

中文翻译：

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优化血小板分泌组以提供强大的组织特异性再生。

促进细胞增殖是大多数组织再生疗法的基石。由于基于血小板的应用促进了细胞分裂，并且可以针对组织的特定功效进行定制，因此这使其成为开发新型再生疗法的强大候选者。因此，本研究的目的是确定是否可以优化血小板释放物以促进特定组织的细胞增殖和分化。剖析了血小板释放物中的生长因子的生理和超生理血小板浓度。我们分析了生理和生理上的释放对C2C12骨骼肌成肌细胞，H9C2大鼠心肌细胞，人皮肤成纤维细胞（HDF），HaCaT角质形成细胞和软骨细胞的影响。通过增殖测定，mRNA，和蛋白质表达。我们表明，超生理释放不是简单的生理释放的浓缩版本。生理释放促进了C2C12，HDF和软骨细胞增殖，而对H9C2或HaCaT细胞没有影响。与生理释放相比，超生理释放引起C2C12和HDF细胞更强的增殖。重要的是，超生理释放诱导了H9C2细胞的增殖。骨骼肌和心肌细胞的增殖作用部分受血管内皮生长因子α驱动。此外，超生理释放诱导H9C2和C2C12，HDF和角质形成细胞的分化。这项研究提供了有关释放促进肌肉，心脏，皮肤，