The influence of platelet-rich plasma as hematoma-mimicking environment on behavior and function of human bone marrow mesenchymal stromal cells

Mesenchymal stromal cells (MSCs), identifiable by their plastic adherence and specific cluster of differentiation (CD) markers, can differentiate into osteoblasts, adipocytes and chondroblasts. They can be sourced from various origins with bone marrow MSCs exhibiting the most diverse multilineage differentiation. Bone fractures involve a complex healing process where MSCs play a crucial role, particularly in relation to their immunomodulatory properties. MSCs interact with the immune system, especially macrophages and T cells, to modulate the inflammatory response and promote the timely transition from inflammation to tissue healing processes. Increasingly used in cell-based therapies due to their easy transplantation, diverse sources, regenerative capacity, and immunomodulatory effects, MSCs show promising outcomes in clinical trials for various diseases. However, their clinical application faces challenges such as low efficiency, poor survival of transplanted cells, and issues regarding cell localization, showing the need for a better understanding of MSCs in inflammatory environments. Platelet-rich plasma (PRP) is investigated to enhance MSC treatments, harnessing its growth factors and cytokines which might be able to mimic the hematoma environment in tissue repair. In this study, MSCs were examined under the influence of soluble factors derived from conditioned media (CM) of PRP hydrogels. Effects were compared with CM derived from fibrinogen as another component of the hematoma. Survival and division rates, apoptosis and autophagy mechanisms, as well as cell migration and motility under PRP-CM and FBR-CM treatments, were assessed, using various assays. Results showed a significant increase in migration and motility under PRP-CM influence, potentially mediated through the PI3K/Akt/mTOR signaling pathway. Survival and apoptosis were unaffected. Moreover, an influence on autophagy-related gene expression was observed, suggesting a need for further investigation. These findings show that the inflammatory environment simulated by PRP-CM affects intracellular metabolic processes, particularly the migration and motility behaviors of MSCs. The outcomes highlight the importance of elucidating MSC metabolism and intracellular activation of different signaling pathways in inflammatory environments.