Author | Evangelista, Afrânio Ferreira | |
Author | Santos, Marcos André Vannier dos | |
Author | Silva, Gessica Sabrina de Assis | |
Author | Silva, Daniela Nascimento | |
Author | Juiz, Paulo José Lima | |
Author | Nonaka, Carolina Kymie Vasques | |
Author | Santos, Ricardo Ribeiro dos | |
Author | Soares, Milena Botelho Pereira | |
Author | Villarreal, Cristiane Flora | |
Access date | 2018-08-14T12:46:12Z | |
Available date | 2018-08-14T12:46:12Z | |
Document date | 2018 | |
Citation | EVANGELISTA, A. F. et al. Bone marrow-derived mesenchymal stem/stromal cells reverse the sensorial diabetic neuropathy via modulation of spinal neuroinflammatory cascades. Journal of Neuroinflammation, v. 15, p. 189, 2018. | pt_BR |
ISSN | 1742-2094 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/28118 | |
Sponsorship | National Institutes of Health guide for the care and use of Laboratory animals (NIH, 8023) and the Institutional Animal Care and Use Committee FIOCRUZ (CPqGM 025/2011) | pt_BR |
Language | eng | pt_BR |
Publisher | BioMed Central | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Células tronco | pt_BR |
Subject in Portuguese | Neuropatia sensorial | pt_BR |
Subject in Portuguese | Diabetes | pt_BR |
Subject in Portuguese | Medula espinhal | pt_BR |
Subject in Portuguese | Neuroinflamação | pt_BR |
Subject in Portuguese | Galectina-3 | pt_BR |
Title | Bone marrow-derived mesenchymal stem/stromal cells reverse the sensorial diabetic neuropathy via modulation of spinal neuroinflammatory cascades | pt_BR |
Type | Article | pt_BR |
DOI | 10.1186/s12974-018-1224-3 | |
Abstract | Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction. Methods: C57Bl/6 mice were treated with bone marrow-derived MSC (1 × 106), conditioned medium from MSC
cultures (CM-MSC) or vehicle by endovenous route following the onset of streptozotocin (STZ)-induced diabetes.
Paw mechanical and thermal nociceptive thresholds were evaluated by using von Frey filaments and Hargreaves
test, respectively. Morphological and morphometric analysis of the sciatic nerve was performed by light microscopy
and transmission electron microscopy. Mediators and markers of neuroinflammation in the spinal cord were
measured by radioimmunoassay, real-time PCR, and immunofluorescence analyses.
Results: Diabetic mice presented behavioral signs of sensory neuropathy, mechanical allodynia, and heat
hypoalgesia, which were completely reversed by a single administration of MSC or CM-MSC. The ultrastructural
analysis of the sciatic nerve showed that diabetic mice exhibited morphological and morphometric alterations,
considered hallmarks of DN, such as degenerative changes in axons and myelin sheath, and reduced area and
density of unmyelinated fibers. In MSC-treated mice, these structural alterations were markedly less commonly
observed and/or less pronounced. Moreover, MSC transplantation inhibited multiple parameters of spinal
neuroinflammation found in diabetic mice, causing the reduction of activated astrocytes and microglia,
oxidative stress signals, galectin-3, IL-1β, and TNF-α production. Conversely, MSC increased the levels of
anti-inflammatory cytokines, IL-10, and TGF-β.
Conclusions: The present study described the modulatory effects of MSC on spinal cord neuroinflammation
in diabetic mice, suggesting new mechanisms by which MSC can improve DN. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | Federal University of Bahia. Pharmacy College. Salvador, BA, Brasil | pt_BR |
Affilliation | São Rafael Hospital. Center of Biotechnology and Cell Therapy. Salvador, BA, Brazil | pt_BR |
Affilliation | Federal University of Recôncavo of Bahia. Feira de Santana, BA, Brazil | pt_BR |
Affilliation | São Rafael Hospital. Center of Biotechnology and Cell Therapy. Salvador, BA, Brazil | pt_BR |
Affilliation | São Rafael Hospital. Center of Biotechnology and Cell Therapy. Salvador, BA, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotechnology and Cell Therapy. Salvador, BA, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Pharmacy College. Salvador, BA, Brasil | pt_BR |
Subject | Stem cells | pt_BR |
Subject | Sensory neuropathy | pt_BR |
Subject | Diabetes | pt_BR |
Subject | Spinal cord | pt_BR |
Subject | Neuroinflammation | pt_BR |
Subject | Galectin-3 | pt_BR |