Aplicação de nanopartículas no modelo experimental murino de transplante intrauterino de células hematopoiéticas

• Ano de defesa: 2016
• Autor(a) principal: Fachin, Camila Girardi [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Hematopoietic stem cell transplantation; Fetal therapy; Nanoparticles; Transplante de células-tronco hematopoéticas; Terapia fetal
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4096273; https://repositorio.unifesp.br/handle/11600/46951

Introduction: In utero hematopoietic cell transplantation (IUHCT) has tremendous potential for prenatal treatment of congenital hematological disorders, but clinical application has been limited by low engraftment levels. Host cell competition is one of the most formidable barriers to successful engraftment post IUHCT. Aim: To increase donor host competitiveness and engraftment level post IUHCT by using nanoparticles derived from platelets (NPP) or synthetic nanoparticles loaded with CHIR99021, a glycogen synthase kinase-3 enzyme (GSK-3) inhibitor. Methods: Bone marrow mononuclear cells (BM-MNC) were isolated from B6-GFP or Pepboys adult mice. NPP were produce from B6-GFP whole blood. CHIR99021 loaded multilamelar lipid vesicles (MLV) were synthesized from liposomes. Previously to IUHCT, donor cells were incubated with NPP or MLV. Donor cell engraftment was assessed in recipient blood for up to 6 months following birth by flow cytometry. Results: Animals that received NPP treated cells had a higher chimerism at 1 month (NPP 19,5±12.7% vs control 12±5,6%, teste t p<0,05), but after 3 months chimerism droped (6 months: NPP 2,9±2,3% vs control 3,8±2,4%, teste t p>0,05). Animals that received MLV- CHIR99021 treated cells had a very high (therapeutic) sustained chimerism until 6 months of life (MLV 48,5±3,1% vs control 3,4±0,7%, teste t p<0,0001). Conclusion: Cell engineering with MLV- CHIR99021 enhances engraftment of BM-MNC following IUHCT to therapeutic levels.