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Evaluation of skin heterologous graft using acellular matrices obtained from porcine skin and Annexin A1 action as anti-inflammatory / immunosuppressive agent

Grant number: 12/13041-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2012
Effective date (End): February 29, 2016
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Sonia Maria Oliani
Grantee:Kallyne Kioko Oliveira Mimura
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The loss of skin and appendages, is a non-healing wounds or from complications surgical, excision of complicated hernias, cancer or severe burns, has created a great expectation for new technologies in the field of tissue engineering. The advances in this area have led to the development of several products (synthetic and biological) for use in transplants, with the goal of improving patient's quality of life through the restoration and maintenance of tissues and the tissues function and organs transplanted. Designated as skin substitutes, equivalents of the epidermis and dermis have been investigated and used clinically for several years. However, acellular biological materials that are immunologically compatible and suited to the repair of skin, either as a fill (dermis) or support and protection (epidermis), must be carefully implemented. Thus, our goal will be to standardize a technique economically viable decellularization skin, develop acellular (scaffolds) and characterize them in terms of biochemical, biomechanical and structural. To evaluate the biocompatibility of the scaffolds we will do a first experiment with the subcutaneous implantation of scaffolds in rats. In another experiment, we will perform the transplantation of scaffolds, with or without treatment with the protein annexin A1 (AnxA1) and the immunosuppressant cyclosporin. Also evaluate the following aspects: the biocompatibility of implants / transplants to the host tissue (healing process, integration of the implant, host cell density in implant, presence of mast cells and mineralization of subcutaneous implantation); AnxA1 protein expression in leukocytes located in heterografts; the process of apoptosis and neovascularization respectively by the expressions of AnxA5 and Von Willebrand factor, the regenerative potential of the scaffolds and immunogenic in different experimental conditions by means of phenotypic macrophage M1/M2, the gene expression of growth factors FGF and TGF; the amount of circulating leukocytes in the peripheral blood, and the dosage of pro-inflammatory cytokines by biochemical analyzes. The AnxA1 will be evaluated as a potential therapeutic option to reduce inflammation and improve healing and regenerative process of the heterograft, possibly with fewer side effects compared to traditional therapy.

Scientific publications (4)
(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)
LACERDA, JESSICA ZANI; DREWES, CARINE CRISTIANE; OLIVEIRA MIMURA, KALLYNE KIOKO; ZANON, CAROLINE DE FREITAS; ANSARI, TAHERA; GIL, CRISTIANE DAMAS; GRECO, KARIN VICENTE; POLISELLI FARSKY, SANDRA HELENA; OLIANI, SONIA MARIA. Annexin A1(2-26) Treatment Improves Skin Heterologous Transplantation by Modulating Inflammation and Angiogenesis Processes. FRONTIERS IN PHARMACOLOGY, v. 9, SEP 10 2018. Web of Science Citations: 1.
COSTA, MAURICIO B.; MIMURA, KALLYNE K. O.; FREITAS, ALINE A.; HUNGRIA, EMERITH M.; SOUSA, ANA LUCIA O. M.; OLIANI, SONIA M.; STEFANI, MARIANE M. A. Mast cell heterogeneity and anti-inflammatory annexin A1 expression in leprosy skin lesions. Microbial Pathogenesis, v. 118, p. 277-284, MAY 2018. Web of Science Citations: 0.
MIMURA, KALLYNE K. O.; MORAES, ANDREIA R.; MIRANDA, ALINE C.; GRECO, REBECCA; ANSARI, TAHERA; SIBBONS, PAUL; GRECO, KARIN V.; OLIANI, SONIA M. Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling. SCIENTIFIC REPORTS, v. 6, OCT 11 2016. Web of Science Citations: 10.
PARRA TEIXEIRA, RODRIGO ANTONIO; OLIVEIRA MIMURA, KALLYNE KIOKO; ARAUJO, LEANDRO PIRES; GRECO, KARIN VICENTE; OLIANI, SONIA MARIA. The essential role of annexin A1 mimetic peptide in the skin allograft survival. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, v. 10, n. 2, p. E44-E53, FEB 2016. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.