europrotection and gliosis attenuation by intravenous application of human mesenchymal stem cells (hMSC) following ventral root crush in mic

Author(s)

Cartarozzi, Luciana Politti ^[1] ; Perez, Matheus ^[2] ; Fernandes, Gabriel Gripp ^[3] ; Chiarotto, Gabriela Bortolanca ^[1] ; Luzo, Angela Cristina Malgeiros ^[4] ; Campos, Alline Cristina ^[3] ; Kirchhoff, Frank ^[5] ; de Oliveira, Alexandre Leite Rodrigues ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Lab Nerve Regenerat, Cidade Univ Zeferino Vaz, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Av Bandeirantes 3900, BR-14040907 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Av Bandeirantes 3900, BR-14040907 Ribeirao Preto, SP - Brazil

^[4] Univ Campinas Hemoctr Unicamp, Inst Nacl Ciencia & Tecnol Sangue, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil

^[5] Univ Saarland, Ctr Integrat Physiol & Mol Med CIPMM, Mol Physiol, Bldg 48, D-66421 Homburg - Germany

• Document type: Journal article
• Source: Molecular and Cellular Neuroscience; v. 118, JAN 2022.
• Web of Science Citations: 0

Abstract

Rupture and stretching of spinal roots are common incidents that take place in high-energy accidents. The proximal axotomy of motoneurons by crushing of ventral roots is directly related to the degeneration of half of the lesioned population within the first two weeks. Moreover, only a small percentage of surviving motoneurons can successfully achieve regeneration after such a proximal lesion, and new treatments are necessary to improve this scenario. In this sense, mesenchymal stem cells (MSC) are of great interest once they secrete a broad spectrum of bioactive molecules that are immunomodulatory and can restore the environment after a lesion. The present work aimed at studying the effects of human mesenchymal stem cells (hMSC) therapy after ventral root crush (VRC) in mice. We evaluated motoneuron survival, glial reaction, and synapse preservation at the ventral horn. For this purpose, C57BL/6 J were submitted to a crush procedure of L4 to L6 ventral roots and treated with a single intravenous injection of adipose-derived hMSC. Evaluation of the results was carried out at 7, 14, and 28 days after injury. Analysis of motoneuron survival and astrogliosis showed that hMSC treatment resulted in higher motoneuron preservation (motoneuron survival ipsi/contralateral ratio: VRC group = 53%, VRC + hMSC group = 66%; p < 0.01), combined with reduction of astrogliosis (ipsi/contralateral GFAP immunolabeling: VRC group = 470%, VRC + hMSC group = 250%; p < 0.001). The morphological classification and Sholl analysis of microglial activation revealed that hMSC treatment reduced type V and increased type II profiles, indicating an enhancement of surveying over activated microglial cells. The glial reactivity modulation directly influenced synaptic inputs in apposition to axotomized motoneurons. In the hMSC-treated group, synaptic maintenance was increased (ipsi/contralateral synaptophysin immunolabeling: VRC group = 53%, VRC + hMSC group = 64%; p < 0.05). Overall, the present data show that intravenous injection of hMSC has neuroprotective and antiinflammatory effects, decreasing reactive astrogliosis, and microglial reaction. Also, such cell therapy results in motoneuron preservation, combined with significant maintenance of spinal cord circuits, in particular those related to the ventral horn. (AU)

• FAPESP's process: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/02714-7 - Involvement of MHC I, TLR2 and TLR4 in the synaptic plasticity and functional reovery following crushing of spinal ventral roots in mice
• Grantee: Luciana Politti Cartarozzi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral