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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). São Paulo , SP, Brazil
City of the host institution:São Paulo
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)

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Scientific publications (20)
(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, . (14/50983-3, 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, . (16/21470-3, 14/50983-3)
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, . (16/21470-3)
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., . (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., . (16/21470-3, 17/17868-4, 19/21070-3)
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, . (16/21470-3, 19/21070-3, 17/17868-4)
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, . (16/21470-3, 14/50983-3)
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., . (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, . (16/21470-3, 17/17868-4, 19/21070-3)
MUNOZ, JUAN MATHEUS; PILEGGI, GIOVANA FONTANELLA; NUCCI, MARIANA PENTEADO; ALVES, ARIELLY DA HORA; PEDRINI, FLAVIA; DO VALLE, NICOLE MASTANDREA ENNES; MAMANI, JAVIER BUSTAMANTE; DE OLIVEIRA, FERNANDO ANSELMO; LOPES, ALEXANDRE TAVARES; CARRENO, MARCELO NELSON PAEZ; et al. In Silico Approach to Model Heat Distribution of Magnetic Hyperthermia in the Tumoral and Healthy Vascular Network Using Tumor-on-a-Chip to Evaluate Effective Therapy. PHARMACEUTICS, v. 16, n. 9, p. 21-pg., . (16/21470-3, 24/03247-1, 19/21070-3, 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, . (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, . (15/25923-0, 16/17961-1, 16/21470-3)
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, . (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, . (16/21470-3, 14/50983-3)
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., . (19/21070-3, 16/21470-3, 17/17868-4)
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., . (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., . (16/21470-3, 17/17868-4, 19/21070-3)
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., . (16/21470-3, 17/17868-4, 19/21070-3)
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, . (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, . (16/21470-3, 14/50983-3)