Células mesenquimais estromais e Fator de crescimento derivado de plaquetas: caracterização e potencial terapêutico em lesões associadas à doença falciforme

Abstract

Osteonecrosis and leg ulcers are tissue injuries associated with microvascular complications commonly found in patients with sickle cell disease (SCD). Since these comorbidities have limited treatment options, the use of mesenchymal stromal cells or growth factors may be an effective therapeutic approach for treating osteonecrosis and chronic leg ulcers in patients with sickle cell disease, improving clinical outcomes and accelerating tissue healing. This study aimed to quantify the population of mesenchymal stromal cells in bone marrow samples from patients with SCD and osteonecrosis and compare it with patients with osteoarticular complications not related to SCD, as well as to investigate the effects of human recombinant PDGF-BB (rh-PDGF) on the wound healing process in a murine model of SCD. Our first study revealed that the population of CD271+CD45-/low mesenchymal stromal cells was higher in both the total aspirate and the bone marrow mononuclear cell concentrate in patients with SCD and osteonecrosis compared to patients with osteoarticular complications not related to SCD. We demonstrated a significant correlation (r = 0.7483; p = 0.0070) between the number of CD271+CD45-/low cells and the colony-forming unit-fibroblast (CFU-F) count in vitro in samples from SCD patients. Our data revealed that the application of PDGF-BB contributed to greater wound closure on day 3 post-injury (46.71 ± 3.87%) vs (33.82 ± 2.72%) in wounds treated with PBS. Wounds treated with PDGF showed greater collagen deposition and an increase in the number of blood vessels and perivascular cells on day 3 post-injury. However, there was a higher presence of inflammatory infiltrate in PDGF-treated wounds, corroborating the elevated levels of pro-inflammatory mediators found in gene expression analyses. In conclusion, these studies demonstrate the promising potential of applying mesenchymal stromal cells and growth factors in the treatment of microvascular complications related to sickle cell disease.