PHENOTYPIC AND FUNCTIONAL STUDY OF KERATINOCYTES EXPOSED TO SERUM OF SYSTEMIC SCLEROSIS PATIENTS TREATED WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

• Grant number: 22/01429-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Carolina de Oliveira Rodrigues
• Grantee: Djúlio César Zanin da Silva
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 23/04897-7 - Investigating the interplay between skin fibroblasts and immune cells in systemic sclerosis patients using tissue engineering approaches, BE.EP.DR

Abstract

Systemic sclerosis (SSc) is an autoimmune disease marked by fibrosis of the skin and internal organs, immune dysregulation and vasculopathy. Autologous hematopoietic stem cell transplantation (AHSCT) has been investigated as treatment for patients with severe and progressive SSc. Although patients show great clinical and histopathological improvement of cutaneous fibrosis after transplantation, little is known about the cellular and molecular mechanisms involved, especially in the context of the inflammation-fibrosis axis. Thus, the objective of the present study is to determine how AHSCT affects the phenotype and functionality of keratinocytes (directly involved in the pathological inflammation-fibrosis axis) and how these alterations are associated with the clinical status of patients with SSc. This study has a retrospective and prospective longitudinal design, and will include serological analysis (ELISA and Multiplex) and gene expression analysis in skin biopsies of patients with SSc undergoing AHSCT at the Bone Marrow Transplantation Unit of HCFMRP-USP. Clinical data will be retrieved from patients' medical records. In the laboratory, the HaCaT keratinocyte cell line will be exposed to serum samples collected from SSc patients before and after AHSCT, and analyzed for phenotypic, functional, gene and protein expression changes. We believe that since AHSCT halts autoreactive and inflammatory pathogenic responses, serum samples from transplanted patients will show a reduction in fibroinflammatory stimuli, reflecting more adequate keratinocyte functionality and less skin involvement in patients. Thus, the study may provide scientific bases to understand the effects of AHSCT on fibrosis in patients with SSc.