Romano, Serena (2025) IDENTIFICATION OF PREDICTIVE FACTORS IN PLATELET- RICH PLASMA AND MESENCHYMAL STEM CELLS FOR REGENERATIVE MEDICINE APPLICATION. [Tesi di dottorato]

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Abstract

Regenerative medicine represents a promising medical science field, focusing on repairing, replacing or regenerating damaged tissues and organs. Among the most promising strategies are Autologous Platelet Concentrates (APCs), widely used for the infiltrative treatment of Knee Osteoarthritis (OA) to improve tissue healing and relieve pain, and Bone Marrow Aspirate Concentrates (BMACs), for the treatment of Critical Limb Ischemia (CLI). APCs have demonstrated potential in enhancing tissue healing by promoting cell proliferation, angiogenesis, and collagen synthesis, making them valuable in musculoskeletal injuries, chronic wounds, and cartilage repair. BMACs, a source of mesenchymal stem cells and hematopoietic progenitors, offer significant regenerative capabilities, particularly in orthopedic and cartilage repair, through cell differentiation and tissue remodeling. My doctoral thesis focuses on two studies. In both cases, a panel of cytokines, chemokines, and growth factors (GFs) was determined to identify biomarkers predictive of clinical outcome in grade I OA and CLI patients. In Study 1, the Numeric Pain Rating Scale (NPRS) was evaluated as a clinical readout before and after APC infiltrations. Lower white blood cell count (WBC) and higher Monocyte-chemoattractant Protein-1 levels in peripheral blood (PB) were associated with APC-induced pain relief. Platelet- derived Growth Factor (PDGF) levels in APC were significantly higher in OA patients displaying larger NPRS reduction, independently of platelet count. Finally, simultaneous determination of PDGF, Vascular Endothelial Growth Factor, and Macrophage Inflammatory Protein-1α in APC discriminated OA patients with very poor and no response. Thus, platelet-released GFs rather than platelet count may predict clinical outcomes in grade 1 knee OA. In Study 2, bone marrow (BM) samples were collected before and after cell concentration with the Sepax-2 instrument. In parallel, peripheral blood (PB) samples were collected at baseline (T0). Treadmill Test and Transcutaneous partial pressure of oxygen were evaluated as clinical outcomes. POST-SEPAX samples showed a statistically significant increase in cell count and viability compared to PRE-SEPAX samples. Inflammatory cytokines such as IL-1ra, IL-8, IL-10 and growth factors such as bFGF, gCSF, and PDGF were found at higher concentrations in BM compared to PB. In bone marrow POST-SEPAX, among the released factors, IL-2 and TNF-α concentrations, negatively correlated with TpcO2. This study confirmed the useful application of stem cell therapy in improving pain and revascularization in patients affected by CLI and promoted soluble factors, such as IL-2 TNF-α, as prognostic factors in the management of pathology.

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