Immunomodulatory mechanisms of mesenchymal stem cells in glial reactivity and correlation with regenerative capacity after lumbar root axotomy

Luciana Politti Cartarozzi

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Author(s):	Luciana Politti Cartarozzi Total Authors: 1
Document type:	Doctoral Thesis
Press:	Campinas, SP.
Institution:	Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:	2018-02-26
Examining board members:	Alexandre Leite Rodrigues de Oliveira; Marimélia Aparecida Porcionatto; Enrico Ghizoni; Antonio Carlos Pinheiro de Oliveira; Thiago Luiz de Russo
Advisor:	Alexandre Leite Rodrigues de Oliveira; Frank Kirchhoff
Abstract
Lesions on CNS/PNS interface are especially severe, leading up to 80% of neuronal degeneration within the first two weeks. Recent data point out to the involvement of MHC-I in the interactions between pre- and post-synaptic neurons, as well as between axotomized neurons and glial cells, having an important role in selective synaptic maintenance after lesion. The present work objectives the stabilization of ventral root crush (VRC) in mice and further treatment with human mesenchymal stem cells (hMSC), evaluating the potential effect of lack of MHC-I on motoneuron survival, glial reaction, and synaptic covering, with and without cell therapy. For this purpose, C57BL/6J WT e beta2mKO mice were submitted to the crush of L4 to L6 ventral roots, treated or not with one intravenous injection of hMSC and kept for 7, 14 and 28 days after injury. Analysis of motoneuron survival and astrogliosis showed similar patterns regarding the increasing loss of motoneurons and astrogliosis over time on WT animals, while the lack of MHC-I increased the motoneuron susceptibility in the acute phase. hMSC treatment resulted in higher motoneuron preservation and astrogliosis control independent of MHC-I. Microglial reaction was more intense 7 days after lesion in WT animals, becoming reduced over time. In the lack of MHC-I, an analogous pattern was detected, only with a microglial reaction 33% more intense in the acute time point after lesion. Synaptic inputs were reduced around axotomized motoneurons from the 7th day after lesion, being acutely more intense on beta2mKO mice, reaching up to 50% reduction 28 days after injury. After hMSC treatment, both in WT and beta2mKO mice, around 65% of synapses were maintained. Results described herein show that after ventral root crush in mice, MHC I plays a role on acute microglial reaction control, affecting temporarily synaptic loss and that hMSC treatment reduced reactive astrogliosis and microglial reaction, causing motoneuron neuroprotection and synaptic covering maintenance independent of the presence of MHC-I (AU)

FAPESP's process:	13/16134-6 - Immunomodulatory mechanisms of mesenchymal stem cells in glial reactivity and correlation with nervous system regenerative capacity after lumbar root axotomy
Grantee:	Luciana Politti Cartarozzi
Support Opportunities:	Scholarships in Brazil - Doctorate

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