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Study of therapeutic potencial of of mesenchymal and embryonary stem cells in Duchenne Muscular Dystrophy murine model

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Author(s):
Danielle Ayub de Barros Guerrieri Pinheiro
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo. , gráficos, ilustrações, tabelas.
Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
Defense date:
Examining board members:
Mariz Vainzof; Lygia da Veiga Pereira Carramaschi; Bryan Eric Strauss
Advisor: Mariz Vainzof
Field of knowledge: Biological Sciences - Genetics
Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP
Location: Universidade de São Paulo. Biblioteca do Instituto de Biociências; IB/M-1334
Abstract

We investigated therapeutic potential of murine mesenchymal and embryonic stem cells in the treatment of Duchenne Muscular Dystrophy. Their ability to regenerate the dystrophic muscle was studied in vitro and in vivo, in the murine mdx model. In culture, bone marrow mesenchymal stem cells (MSC) showed the capacity to fuse and to spontaneously differentiate into muscle fibers, independently of stimulation by contact with other cell types or exposure to miogenic factors in vitro. When injected into affected muscles, MSC expressing GFP protein were detected after 3 days at most, suggesting their elimination after this period. When injected in the systemic via, MSC eGFP were not properly directed to the dystrophic muscle. These cells were also eliminated in the wild strain FVB mice, suggesting that GFP protein could be responsible for this rejection. The embryonic stem cells (ES-line 129) also showed a good miogenic capacity in vitro. When injected into the muscle of immunosuppressed mdx mice, they caused very intense inflammatory reaction and a significant increase of its leg muscle mass. However, this new tissue did not contain cells with muscle fibers characteristics. In systemically injected mice, the ES cells remained in the region of introduction in the tail, showing poor distribution and dissemination into the injured muscle. Specific ES cell line polymorphic markers analysis identified a concentration of at least 30%. This result indicates that muscle hypertrophy observed in injected mice was caused by at least this amount of cells. Additional studies are necessary to increase the therapeutic potential of these cells in dystrophic murine models. (AU)