Therapeutic action of mesenchymal stem cells from human bone marrow labeled with multimodal nanoparticles in diabetic rats subjected to stroke: study of cellular, molecular and functional mechanisms.

• Grant number: 16/21470-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2017
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Lionel Fernel Gamarra Contreras
• Grantee: Lionel Fernel Gamarra Contreras
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated researchers: Alberto Tannús ; Dimas Tadeu Covas ; Fernando Fernandes Paiva ; Javier Bustamante Mamani ; Lucas Eduardo Botelho de Souza ; Luciana Cavalheiro Marti ; Rosalia Mendez-Otero

Abstract

Type 2 diabetes mellitus (DM2) is a very prevalence disease and its incidence is increasing. About 8% of the Brazilian population is affected by this disease. Uncontrolled DM 2 increases the risk of cardiovascular and cerebrovascular disease by 75% in consequence of dyslipidemia and hypertension development and renal impairment. Previous studies indicate that cerebrovascular disorders, such as strokes, are major complications of DM2 causing great morbidity and mortality. Current research efforts focused on elucidating more specific and effective treatments for the regeneration of the ischemic area. Considering this background, the use of mesenchymal stem cells (MSC) in cellular therapy, especially in regenerative medicine, has emerged as a promising therapeutic tool. This kind of therapy approaches a variety of brain diseases owing to the MSC intrinsic capacity to self-renew and differentiate into multiple celllineages, including glial and neuronal cells, which facilitates their isolation, expansion, manipulation and modulation of the inflammatory response. Although the precise cellular and molecular mechanism involved in repair promoted by MSC in experimental studies remains a challenge, the literature clearly demonstrates the potential use of bone marrow cells in stroke models induced by DM2. Thus, this study intends to apply stem cells and nanobiotechnology combined with multifunctional magnetic nanoparticles and molecular imaging techniques to elucidate the mechanisms of treatment and contribute to the diagnosis, therapy and bioengineering advances in the biomedical field. The purpose of this project is to study the cellular and molecular mechanisms and functional repair mediated by MSC in the ischemic brain tissue marked with multimodal nanoparticles in animal models of DM2. The use of nanobiotechnological resources allow the monitorization of these cells in vivo by molecular images techniques, which tracks cells migration and assists thefunctional characterization of these cells in the ischemic brain region of the experimental modelinduced by photothrombosis. (AU)

Scientific publications

(19)

(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)

MAMANI, JAVIER BUSTAMANTE; MARINHO, BRUNA SOUTO; DE ALBUQUERQUE REGO, GABRIEL NERY; NUCCI, MARIANA PENTEADO; ALVIERI, FERNANDO; DOS SANTOS, RICARDO SILVA; MATIAS FERREIRA, JOAO VICTOR; DE OLIVEIRA, FERNANDO ANSELMO; GAMARRA, LIONEL FERNEL. Magnetic hyperthermia therapy in glioblastoma tumor on-a-Chip model. Einstein (São Paulo), v. 18, 2020. (14/50983-3, 16/21470-3)

NUCCI, MARIANA PENTEADO; FILGUEIRAS, IGOR SALERNO; FERREIRA, JOAO MATIAS; DE OLIVEIRA, FERNANDO ANSELMO; NUCCI, LEOPOLDO PENTEADO; MAMANI, JAVIER BUSTAMANTE; REGO, GABRIEL NERY ALBUQUERQUE; GAMARRA, LIONEL FERNEL. Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review. WORLD JOURNAL OF STEM CELLS, v. 12, n. 5, p. 381-405, MAY 26 2020. (16/21470-3)

ALVIERI, FERNANDO; MAMANI, JAVIER B.; NUCCI, MARIANA P.; OLIVEIRA, FERNANDO A.; FILGUEIRAS, IGOR S.; REGO, GABRIEL N. A.; DE BARBOZA, MARYCEL F.; DA SILVA, HELIO R.; GAMARRA, LIONEL F.. Methods of Granulocyte Isolation from Human Blood and Labeling with Multimodal Superparamagnetic Iron Oxide Nanoparticles. Molecules, v. 25, n. 4, FEB 2 2020. (16/21470-3, 14/50983-3)

OLIVEIRA, FERNANDO A.; NUCCI, MARIANA P.; FILGUEIRAS, IGOR S.; FERREIRA, JOAO M.; NUCCI, LEOPOLDO P.; MAMANI, JAVIER B.; ALVIERI, FERNANDO; SOUZA, LUCAS E. B.; REGO, GABRIEL N. A.; KONDO, ANDREA T.; et al. Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model. CELLS, v. 9, n. 4, APR 2020. (16/21470-3, 14/50983-3)

NUCCI, MARIANA P.; OLIVEIRA, FERNANDO A.; FERREIRA, JOAO M.; PINTO, YOLANDA O.; ALVES, ARIELLY H.; MAMANI, JAVIER B.; NUCCI, LEOPOLDO P.; VALLE, NICOLE M. E.; GAMARRA, LIONEL F.. ffect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysi. CELLS, v. 11, n. 3, FEB 2022. (16/21470-3, 19/21070-3, 17/17868-4)

THEINEL, MATHEUS H.; NUCCI, MARIANA P.; ALVES, ARIELLY H.; DIAS, OLIVIA F. M.; MAMANI, JAVIER B.; GARRIGOS, MURILO M.; OLIVEIRA, FERNANDO A.; REGO, GABRIEL N. A.; VALLE, NICOLE M. E.; CIANCIARULLO, GABRIELA; et al. The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments. NUTRIENTS, v. 15, n. 6, p. 34-pg., 2023-03-01. (16/21470-3, 17/17868-4, 19/21070-3)

GARRIGOS, MURILO MONTENEGRO; DE OLIVEIRA, FERNANDO ANSELMO; NUCCI, MARIANA PENTEADO; NUCCI, LEOPOLDO PENTEADO; ALVES, ARIELLY DA HORA; METROPOLO DIAS, OLIVIA FURIAMA; GAMARRA, LIONEL FERNEL. How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models. WORLD JOURNAL OF STEM CELLS, v. 14, n. 8, p. 22-pg., 2022-08-26. (16/21470-3, 17/17868-4, 19/21070-3)

GARRIGOS, MURILO M.; OLIVEIRA, FERNANDO A.; NUCCI, MARIANA P.; MAMANI, JAVIER B.; DIAS, OLIVIA F. M.; REGO, GABRIEL N. A.; JUNQUEIRA, MARA S.; COSTA, CICERO J. S.; SILVA, LUCAS R. R.; ALVES, ARIELLY H.; et al. Bioluminescence Imaging and ICP-MS Associated with SPION as a Tool for Hematopoietic Stem and Progenitor Cells Homing and Engraftment Evaluation. PHARMACEUTICS, v. 15, n. 3, p. 18-pg., 2023-03-01. (16/21470-3, 17/17868-4, 19/21070-3)

MURILO MONTENEGRO GARRIGÓS; FERNANDO ANSELMO DE OLIVEIRA; CÍCERO JÚLIO SILVA COSTA; LUCAS RENAN RODRIGUES; MARIANA PENTEADO NUCCI; ARIELLY DA HORA ALVES; JAVIER BUSTAMANTE MAMANI; GABRIEL NERY DE ALBUQUERQUE REGO; JUAN MATHEUS MUNOZ; LIONEL FERNEL GAMARRA. Assessing the toxicity of one-step-synthesized PEG-coated gold nanoparticles: in vitro and in vivo studies. Einstein (São Paulo), v. 22, 2024-05-20. (17/17868-4, 19/21070-3, 16/21470-3)

OLIVEIRA, FERNANDO A.; NUCCI, MARIANA P.; MAMANI, JAVIER B.; ALVES, ARIELLY H.; REGO, GABRIEL N. A.; KONDO, ANDREA T.; HAMERSCHLAK, NELSON; JUNQUEIRA, MARA S.; DE SOUZA, LUCAS E. B.; GAMARRA, LIONEL E.. Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic-Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model. BIOMEDICINES, v. 9, n. 7, JUL 2021. (14/50983-3, 16/21470-3)

REGO, GABRIEL N. A.; NUCCI, MARIANA P.; MAMANI, JAVIER B.; OLIVEIRA, FERNANDO A.; MARTI, LUCIANA C.; FILGUEIRAS, IGOR S.; FERREIRA, JOAO M.; REAL, CAROLINE C.; FARIA, DANIELE DE PAULA; ESPINHA, PALOMA L.; et al. Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 3, FEB 2020. (16/21470-3, 14/50983-3)

FELIX SOUZA, TAYLLA KLEI; NUCCI, MARIANA PENTEADO; MAMANI, JAVIER BUSTAMANTE; DA SILVA, HELIO RODRIGUES; CARVALHO FANTACINI, DAIANNE MACIELY; BOTELHO DE SOUZA, LUCAS EDUARDO; PICANCO-CASTRO, VIRGINIA; COVAS, DIMAS TADEU; VIDOTO, EDSON LUIS; TANNUS, ALBERTO; et al. Image and motor behavior for monitoring tumor growth in C6 glioma model. PLoS One, v. 13, n. 7, JUL 26 2018. (16/21470-3, 14/50983-3)

DA SILVA, HELIO; NUCCI, MARIANA P.; MAMANI, JAVIER B.; MENDEZ-OTERO, ROSALIE; NUCCI, LEOPOLDO P.; TANNUS, ALBERTO; GAMARRA, LIONEL F.. Evaluation of temperature induction in focal ischemic thermocoagulation model. PLoS One, v. 13, n. 7, JUL 5 2018. (16/21470-3, 14/50983-3)

PESCATORE, LUCIANA A.; GAMARRA, LIONEL F.; LIBERMAN, MARCEL. Multifaceted Mechanisms of Vascular Calcification in Aging. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, v. 39, n. 7, p. 1307-1316, JUL 2019. (15/25923-0, 16/17961-1, 16/21470-3)

VALLE, NICOLE M. E.; NUCCI, MARIANA P.; ALVES, ARIELLY H.; RODRIGUES, LUIZ D.; MAMANI, JAVIER B.; OLIVEIRA, FERNANDO A.; LOPES, CAIQUE S.; LOPES, ALEXANDRE T.; CARRENO, MARCELO N. P.; GAMARRA, LIONEL F.. Advances in Concentration Gradient Generation Approaches in a Microfluidic Device for Toxicity Analysis. CELLS, v. 11, n. 19, p. 56-pg., 2022-10-01. (16/21470-3, 17/17868-4, 19/21070-3)

NUCCI, MARIANA P.; MAMANI, JAVIER B.; OLIVEIRA, FERNANDO A.; FILGUEIRAS, IGOR S.; ALVES, ARIELLY H.; THEINEL, MATHEUS H.; RODRIGUES, LUIZ D.; MARTI, LUCIANA; GAMARRA, LIONEL F.. Optimization of Multimodal Nanoparticles Internalization Process in Mesenchymal Stem Cells for Cell Therapy Studies. PHARMACEUTICS, v. 14, n. 6, p. 23-pg., 2022-06-01. (19/21070-3, 16/21470-3, 17/17868-4)

REGO, GABRIEL NERY DE ALBUQUERQUE; ALVES, ARIELLY DA HORA; NUCCI, MARIANA PENTEADO; MAMANI, JAVIER BUSTAMANTE; DE OLIVEIRA, FERNANDO ANSELMO; GAMARRA, LIONEL FERNEL. Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 12, JUN 2020. (16/21470-3, 14/50983-3)

ALVES, ARIELLY DA HORA; NUCCI, MARIANA PENTEADO; DO VALLE, NICOLE MASTANDREA ENNES; MISSINA, JULIANA MORAIS; MAMANI, JAVIER BUSTAMANTE; REGO, GABRIEL NERY ALBUQUERQUE; DIAS, OLIVIA FURIAMA METROPOLO; GARRIGOS, MURILO MONTENEGRO; DE OLIVEIRA, FERNANDO ANSELMO; GAMARRA, LIONEL FERNEL. Current overview of induced pluripotent stem cell-based blood-brain barrier-on-a-chip. WORLD JOURNAL OF STEM CELLS, v. 15, n. 6, p. 22-pg., 2023-06-26. (16/21470-3, 17/17868-4, 19/21070-3)

MAMANI, JAVIER BUSTAMANTE; MARINHO, BRUNA SOUTO; DE ALBUQUERQUE REGO, GABRIEL NERY; NUCCI, MARIANA PENTEADO; ALVIERI, FERNANDO; DOS SANTOS, RICARDO SILVA; MATIAS FERREIRA, JOAO VICTOR; DE OLIVEIRA, FERNANDO ANSELMO; GAMARRA, LIONEL FERNEL. Magnetic hyperthermia therapy in glioblastoma tumor on-a-Chip model. Einstein (São Paulo), v. 18, p. 8-pg., 2020-01-01. (16/21470-3, 14/50983-3)