Platelet Lysate Induces in Human Osteoblasts Resumption of Cell Proliferation and Activation of Pathways Relevant for Revascularization and Regeneration of Damaged Bone.

Van Thi Nguyen,Ranieri Cancedda,Fiorella Descalzi,Marta Nardini,Alessandra Ruggiu,Maddalena Mastrogiacomo

doi:10.3390/ijms21145123

Abstract

To understand the regenerative effect of platelet-released molecules in bone repair one should investigate the cascade of events involving the resident osteoblast population during the reconstructive process. Here the in vitro response of human osteoblasts to a platelet lysate (PL) stimulus is reported. Quiescent or very slow dividing osteoblasts showed a burst of proliferation after PL stimulation and returned to a none or very slow dividing condition when the PL was removed. PL stimulated osteoblasts maintained a differentiation capability in vitro and in vivo when tested in absence of PL. Since angiogenesis plays a crucial role in the bone healing process, we investigated in PL stimulated osteoblasts the activation of hypoxia-inducible factor 1-alpha (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) pathways, involved in both angiogenesis and bone regeneration. We observed phosphorylation of STAT3 and a strong induction, nuclear translocation and DNA binding of HIF-1α. In agreement with the induction of HIF-1α an enhanced secretion of vascular endothelial growth factor (VEGF) occurred. The double effect of the PL on quiescent osteoblasts, i.e., resumption of proliferation and activation of pathways promoting both angiogenesis and bone formation, provides a rationale to the application of PL as therapeutic agent in post-traumatic bone repair.

Highlights

Regenerative Medicine, which is the reactivation of regeneration pathways to restore tissue structure and function, is the new frontier for the treatment of tissues damaged by trauma or pathologies
Given the cell proliferation induction exerted by the platelet content, platelet derived products such as, platelet rich plasma (PRP) and platelet lysate (PL) obtained by lysis of platelets concentrated in a small volume of plasma, were produced and proposed as fetal calf serum (FCS) replacement, in different cell culture systems
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Summary

Introduction

Regenerative Medicine, which is the reactivation of regeneration pathways to restore tissue structure and function, is the new frontier for the treatment of tissues damaged by trauma or pathologies. The new microenvironment triggers a cascade of events eventually leading to healing of the damaged tissue. During clot formation, plasma turns to serum and platelet activation and degranulation occur, resulting in the release of factors and cytokines promoting cascade events, including resumption of proliferation of some resident cells [1,2]. Considering the in vitro evidence, platelet derivatives were directly adopted in the clinical practice for the treatment of different tissue defects. In spite of existing discrepancies in the literature regarding the use of platelet derived products [3], encouraging results were reported by the PRP use in chronic skin wounds [4,5,6,7], in dental and maxillofacial surgery [8,9], in orthopedics [10,11,12], and in ophthalmology [13,14]. Beneficial effects were shown in Sport Medicine [12,15] and in clinical trials for the treatment of cartilage degenerative diseases performed with either autologous PRP [16] or autologous PL [17]

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Conclusion