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Evaluation of oxidative stress and cell death of renal cells conditioned in vitro to Diabetic Renal Disease after treatment with bone marrow mesenchymal stem cells transfected with the Klotho gene

Grant number: 18/24562-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Érika Bevilaqua Rangel
Grantee:Poliana Evelyn Soinski de Sousa
Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil


Diabetes mellitus (DM) is an epidemiological disease and a major public health problem, affecting people of all ages, sex, and ethnicity. It is estimated that the number of individuals affected by DM in the world are more than 425 million, and it is estimated that 629 million people will be diagnosed with DM in 2040. Due to hyperglycemia and other associated factors, diabetic nephropathy (DN) is one of the main complications caused by DM. It is a multifactorial, progressive disease that involves different cell types, molecules and signaling pathways. It is one of the most common causes of structural and functional abnormalities of the kidney. One of the main factors responsible for the complications of DM, including DN, is oxidative stress, which is caused by an imbalance between the production of reactive oxygen species (ROS) and the capacity for detoxification and damage repair, that is, the production of ROS exceeds the production of antioxidants. A possible strategy for the treatment of DN is cell therapy that has already had its therapeutic potential validated in preclinical models in both acute and chronic renal diseases. The use of bone marrow-derived mesenchymal stem cells (BM-MSCs) is therefore described in several animal models, including DN models. It presents high therapeutic potential and contributes to the improvement of the morphological and functional alterations. In addition, the therapeutic potential of BM-MSCs combined with renal progenitor cells is of great interest, since they can be genetically modified with plasmids. Klotho is an anti-aging protein with anti-oxidative, anti-apoptosis and anti-fibrosis properties. Therefore, this project aims to evaluate cell death and oxidative stress in an in vitro model of different kidney cells cultured in conditioned media characteristic of diabetic renal disease before and after treatment with BM-MSCs therapy transfected with the Klotho gene.

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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)
SAVIO-SILVA, CHRISTIAN; SOINSKI-SOUSA, POLIANA E.; SIMPLICIO-FILHO, ANTONIO; BASTOS, ROSANA M. C.; BEYERSTEDT, STEPHANY; RANGEL, ERIKA BEVILAQUA. Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 4, . (17/23195-2, 18/24562-1, 17/18072-9)
SAVIO-SILVA, CHRISTIAN; SOINSKI-SOUSA, POLIANA EVELYN; BALBY-ROCHA, MARIA THERESA A.; LIRA, ADYNA DE OLIVEIRA; RANGEL, ERIKA BEVILAQUA. Mesenchymal stem cell therapy in acute kidney injury (AKI): review and perspectives. Revista da Associação Médica Brasileira, v. 66, n. 1, p. S45-S54, . (17/23195-2, 17/18072-9, 18/24562-1)
SAVIO-SILVA, CHRISTIAN; BEYERSTEDT, STEPHANY; SOINSKI-SOUSA, POLIANA E.; CASARO, EXPEDITO B.; BALBY-ROCHA, MARIA THERESA A.; SIMPLICIO-FILHO, ANTONIO; ALVES-SILVA, JAMILLE; RANGEL, ERIKA B.. Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease: A Review of the Studies Using Syngeneic, Autologous, Allogeneic, and Xenogeneic Cells. STEM CELLS INTERNATIONAL, v. 2020, . (17/18072-9, 19/12636-3, 18/24562-1)
CHRISTIAN SÁVIO-SILVA; POLIANA EVELYN SOINSKI-SOUSA; MARIA THERESA A BALBY-ROCHA; ÁDYNA DE OLIVEIRA LIRA; ÉRIKA BEVILAQUA RANGEL. Mesenchymal stem cell therapy in acute kidney injury (AKI): review and perspectives. Revista da Associação Médica Brasileira, v. 66, p. s45-s54, . (17/18072-9, 18/24562-1, 17/23195-2)

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