ffect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysi

Author(s)

Nucci, Mariana P. ^{[1, 2]} ; Oliveira, Fernando A. ^[1] ; Ferreira, Joao M. ^[1] ; Pinto, Yolanda O. ^[1] ; Alves, Arielly H. ^[1] ; Mamani, Javier B. ^[1] ; Nucci, Leopoldo P. ^[3] ; Valle, Nicole M. E. ^[1] ; Gamarra, Lionel F. ^[1]

Affiliation

^[1] Hosp Israelita Albert Einstein, BR-05652000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Fac Med, LIM44, BR-05403000 Sao Paulo - Brazil

^[3] Ctr Univ Planalto Cent, BR-72445020 Brasilia, DF - Brazil

• Document type: Journal article
• Source: CELLS; v. 11, n. 3 FEB 2022.
• Web of Science Citations: 0

Abstract

The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was determined using a 3-{[}4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and bioluminescent image (BLI) after lentiviral transduction and MNP labeling. At random, the animals were divided into 5 groups (control-G1, and experimental G2-G5). The photothrombotic stroke induction was confirmed by local blood perfusion reduction and Triphenyltetrazolium chloride (TTC), and MSC in the G3 and G5 groups were implanted after 24 h, with BLI and near-infrared fluorescence image (NIRF) tracking these cells at 28 h, 2, 7, 14, and 28 days. During a 28-day period, the G5 also conducted physical training, whereas the G4 simply did the training. At 0, 7, 14, and 28 days, the animals were functionally tested using a cylinder test and a spontaneous motor activity test. MNP internalization in MSC was confirmed using brightfield and fluorescence microscopy. In relation to G1 group, only 3% of cell viability reduced. The G2-G5 groups showed more than 69% of blood perfusion reduction. The G5 group performed better over time, with a progressive recovery of symmetry and an increase of fast vertical movements. Up to 7 days, BLI and NIRF followed MSC at the damaged site, demonstrating a signal rise that could be connected to cell proliferation at the injury site during the acute phase of stroke. Local MSC therapy mixed with physical activity resulted in better results in alleviating motor dysfunction, particularly during the acute period. When it comes to neurorehabilitation, this alternative therapy could be a suitable fit. (AU)

• FAPESP's process: 16/21470-3 - 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.
• Grantee: Lionel Fernel Gamarra Contreras
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/21070-3 - Evaluation of the therapeutic efficacy of physical activity-associated nanoparticle-labeled stem cells in the focal ischemia model
• Grantee: João Victor Matias Ferreira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/17868-4 - Therapeutic action of mesenchymal stem cells of the human bone marrow, marked with multimodal nanoparticles, in diabetic rats submitted to focal cerebral ischemia: study of cellular, molecular and functional mechanisms
• Grantee: Yolanda Oliveira Pinto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation