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Título/Title/Titulo

Recombinant Human Growth Factors (PDGF, TGF-β, VEGFs, BMPs) as an Effective Alternative to Platelet-Rich Plasma (PRP) for Tissue Regeneration

Introdução/Introduction/Introdución

Platelet Rich Plasma (PRP) is a blood cell derived product obtained by centrifugation, which contains a high concentration of growth factors in a small volume of plasma. Its major components include: Platelet-derived Growth Factors (PDGF), Transforming Growth Factors (TGF-β 1 and 3), Fibroblast Growth Factors (FGF) and Vascular Endothelial Growth Factors (VEGF) and Bone Morphogenetic Proteins (BMPs), responsible for the osteoinductive activity of the organic bone matrix identified as being members of the TGF-β family. By applying PRP at the site of injury, a robust healing response is achieved. Since 1950s, PRP application has been widely used in several areas such as Orthopedics, Dentistry, Cardiology, Ophthalmology, Dermatology for use in complex chronic wound repair, especially in diabetic patients or patients with venous complications, mucosal wounds, connective tissues, pathologies of the musculoskeletal system, fracture surface, bone graft, among others. In scarring and deficient tissues, there is an impairment of the ideal levels of growth factors in the wound healing phases. Therefore, it is important to maintain adequate levels of growth factors in all the different stages of tissue repair. The preparation of PRP is a non-standard procedure and variable results are being observed in the literature, due to the amount of growth factors and/or methods of preparation. Besides that, usually more than one PRP application is required involving a new blood collection for each application in order to accelerate tissue regeneration. The blood collections are invasive for the patient, being expensive in time and labor in the operational procedure, implying in the increase of the cost. The early preparation of PRP with possibility of storage for use in future applications during treatment could be an important solution to avoid the discomfort of patients; however, the problem of the absence of a gold protocol stays.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

Recombinant growth factors were produced in a safe and reproductive heterologous system using mammalian cells (HEK293, 293T, CHO) to obtain overproducing cell clones, to guarantee their quality and post-translational modifications, which are important for their production or stability. In sequence, the growth factors were purified using heparin affinity chromatography and tested using a specific in vitro biological activity assays for each growth factor. The rhPDGF-BB, rhVEGF, rhTGF-β growth factors application and human PRP were tested in a model of dorsal wound healing in rats or mice (normal and diabetic animals induced with streptozotocin). rhBMPs were applied subcutaneously to induce ectopic bone formation in nude rats. The results showed comparative efficacies in the treatments of wounds with rhPDGF-BB, rhVEGF, rhTGF-β in comparison with PRP application, without significant differences, indicating that the use of recombinant growth factors are so effective as the application of PRP for the tissue regeneration process, as observed in the new tissue with collagen deposition and granulation tissue formation.

Considerações Finais/Final considerations/Consideraciones finales

This work shows the possibility of substitute the PRP application using a safe, effective and reproductive source of growth factors using a mammalian cell platform.

Palavras-chave/Key words/Palabras clave

Platelet-Rich Platelet. Tissue Regeneration. Wounds Healing. Growth Factors. Bone Morphogenetic Protein. Platelet-Derived Growth Factor.

Área

Cell Therapy

Autores

ANA CLAUDIA OLIVEIRA CARREIRA, Gabriella Christina Gonçalves Manini de Paula, Bruna Andrade Aguiar , Rosiléia de Azevedo Campos , Gabriel Levin, Gustavo Gross Belchior, Mari Cleide Sogayar