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Evaluation of Transformation Potential After adoptive transfer of reprogrammed B-1 Lymphocytes

Grant number: 25/07710-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date: August 01, 2025
End date: July 31, 2026
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Anuska Marcelino Alvares Saraiva
Grantee:Nicole Erculana Phelippe
Host Institution: Vice-Reitoria de Pesquisa e Pós-Graduação. Universidade Paulista (UNIP). São Paulo , SP, Brazil

Abstract

Introduction: B-1 lymphocytes are well-known for their ability to differentiate into plasmocytes and secrete natural IgMs, but research has demonstrated their pluripotent potential, allowing them to differentiate into other cell types. A 2015 study revealed that these cells are capable of producing insulin and controlling glycemic levels in diabetic mice. In that experiment, XID mice with STZ-induced diabetes were used, and the transfer of these cells conferred resistance to the disease. General Objective: To evaluate the occurrence of neoplasms in diabetic mice after the adoptive transfer of metabolically reprogrammed B-1 lymphocytes. Methodology: The metabolic reprogramming protocol of B-1 lymphocytes will be performed by culturing adherent peritoneal cells and stimulating them with a combination of crotoxin, nicotinamide, and different high concentrations of glucose, making them insulin-producing cells. The metabolically reprogrammed B-1 cells will be transferred at two different time points to diabetic XID mice, immediately after STZ treatment or upon the establishment of the diabetic condition, and will be subsequently euthanized 7 and 14 days after the transfer of reprogrammed B-1 cells. The glycemia of the animals will be evaluated, and thus, the efficiency of the cell therapy will be determined by the normoglycemic character of the individuals. Considering the success of the therapy, the best date for cell transfer will be chosen, and this condition will be reproduced for the follow-up of the adoptively transferred animals or their diabetic controls for a period of 120 days, after which they will be euthanized. Organs such as the brain, heart, lungs, liver, kidneys, pancreas, and spleen will be collected from all experimental animals for histopathological evaluation to investigate the presence of malignant cells or morphological alterations suggestive of tumor occurrence. The data obtained may significantly contribute to the advancement of cell therapy aimed at glycemic control in diabetic patients, using B-1 lymphocytes. (AU)

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