In vitro Immunomodulation of mesenchymal stem cells in Golden Retriever healthy and affected dogs by muscular dystrophy.

• Grant number: 11/13030-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2011
• Effective date (End): February 28, 2014
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal researcher: Carlos Eduardo Ambrósio
• Grantee: Dilayla Kelly de Abreu
• Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated research grant: 07/51222-2 - Interaction of cell and gene therapy for the correction of Duchenne muscular dystrophy using chimeric endonucleases, AP.JP

Abstract

Duchenne muscular dystrophy (DMD) is a hereditary progressive neuromuscular alteration affecting human males. It is recessive X-linked and is caused by the absence or dysfunction of dystrophin, a protein found in a variety of tissues, mainly in skeletal and cardiac muscle, nerve and specific regions of the nervous system. The canine model Golden Retriever Muscular Dystrophy (GRMD) is more animal similar to DMD, and is considered an experimental model for studies of new therapeutic approaches and better understanding of pathophysiology this disease. Because it is genetically homologous, shares its frame of severe myopathy and lethal clinical development. The process of progressive muscular dystrophy is related to changes in cell populations that make up the immune system of patients, because due to the absence of dystrophin in the sarcoplasmic membrane, the muscle becomes more susceptible to damage, and in its occurrence, a release of cytokines, which stimulate liver cells to secrete acute phase proteins, and promote a co-stimulation of T lymphocytes. The use of stem cells has become an alternative for the treatment of various chronic diseases, are undifferentiated cells able to differentiate and generate progenitors mature and fully differentiated effector cells.The mesenchymal stem cells (MSCs) reside in primary bone marrow and other tissues and is capable of self renewal for multilineage differentiation. MSCs derived from different tissues express markers of developing mesenchymal, endothelial and hematopoietic tissues, but also produce molecules involved in immune system regulation, such as antigens, MHC class I and a variety of cytokines and may thus regulate the immune response. The ease of isolation, expansion of MSC in vivo, combined with its immunomodulatory properties and its safety in a wide variety of clinical trials, makes these cells become promising in the use of cell therapy. However, little is known about the immune response of dogs affected by the disease before cell therapy. The proposed study was produced in order to bring subsidies for feasibility experiments of cellular therapy and treatment of this disease through knowledge about the immunomodulation of immune responses during treatment in vitro with mesenchymal stem cells, contributing to a possible therapeutic application in humans.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOUZA, CAROLINA C. Immunophenotyping lymphocyte and acute phase proteins in canine X-linked muscular dystrophy. Anais da Academia Brasileira de Ciências, v. 90, n. 3, p. 2977-2990, JUL-SEP 2018. Web of Science Citations: 1.

DILAYLA K. DE ABREU; JANAINA M. MONTEIRO; CAROLINA C. SOUZA; RAFAEL G. KARAM; RENATA A. FERNANDES; THAIS B. LESSA; JOSÉ J. FAGLIARI; MARIA ANGELICA MIGLINO; CARLOS EDUARDO AMBROSIO. Immunophenotyping lymphocyte and acute phase proteins in canine X-linked muscular dystrophy. Anais da Academia Brasileira de Ciências, v. 90, n. 3, p. -, Set. 2018.