Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions

• Grant number: 14/06892-3
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2014
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Sergiy Kyrylenko
• Associated scholarship(s): 16/25478-9 - Neuroprotective and immunomodulatory effect of dimethyl-fumarate (DMF) after avulsion and reimplantation of spinal motor roots, BP.MS

Abstract

Recent studies have demonstrated the great neuroprotective potential of stem cells (SC), when engrafted to the nervous system following lesion. The use of adult SCs represents great advantage over the embryonic counterpart, especially due to the easy availability. Nevertheless, embryonic SCs display a plethora of effects, including the ability to differentiate into cells from different germ layers. In this way, the present project proposes to investigate the influence of mesenchymal stem cell engrafting into the spinal cord microenvironment following nerve root lesion or after perforation of the lateral funiculus. Additionally, fibrin sealant will be used as a scaffold for the SCs. Results will be analyzed by qRT-PCR, for VEGF, IL4, IL3, TNF±, IL6, arginase-1, iNOS, and TGF². Microglial reaction and macrophage influx will be studied by immunohistochemistry against Iba-1 and arginase, respectively. Fluorescent in situ hybridization will be employed to confirm the PCR data. Altogether, the present proposal will provide substrate for future therapeutic use of SC therapy following spinal cord injury, improving neuronal survival and regeneration. (AU)

Scientific publications

(32)

(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)

BARBIZAN, ROBERTA; CASTRO, MATEUS V.; FERREIRA, JR., RUI SEABRA; BARRAVIERA, BENEDITO; OLIVEIRA, ALEXANDRE L. R.. Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 15, n. 11, p. 19535-19551, NOV 2014. (14/06892-3, 12/08101-8, 11/23236-4, 09/53846-9)

DE CASTRO, MATEUS VIDIGAL; BARBIZAN, ROBERTA; FERREIRA, JR., RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Direct Spinal Ventral Root Repair following Avulsion: Effectiveness of a New Heterologous Fibrin Sealant on Motoneuron Survival and Regeneration. NEURAL PLASTICITY, 2016. (14/06892-3, 13/04409-0)

MOZAFARI, ROGHAYEH; KYRYLENKO, SERGIY; CASTRO, MATEUS VIDIGAL; FERREIRA, JR., RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, APR 12 2018. (14/06892-3, 13/22045-6)

ARAUJO, MARTA ROCHA; KYRYLENKO, SERGIY; SPEJO, ALINE BARROSO; CASTRO, MATEUS VIDIGAL; FERREIRA JUNIOR, RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion. Experimental Neurology, v. 294, p. 45-57, AUG 2017. (14/06892-3, 12/20456-6, 13/22045-6, 13/23030-2)

BOMBEIRO, ANDRE L.; SANTINI, JULIO C.; THOME, RODOLFO; FERREIRA, ELISANGELA R. L.; NUNES, SERGIO L. O.; MOREIRA, BARBARA M.; BONET, IVAN J. M.; SARTORI, CESAR R.; VERINAUD, LIANA; OLIVEIRA, ALEXANDRE L. R.. Enhanced Immune Response in Immunodeficient Mice Improves Peripheral Nerve Regeneration Following Axotomy. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 10, JUN 14 2016. (14/06892-3, 12/20456-6, 11/08712-4)

CARTAROZZI, LUCIANA POLITTI; RIEDER, PHILLIP; BAI, XIANSHU; SCHELLER, ANJA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; KIRCHHOFF, FRANK. In vivo two-photon imaging of motoneurons and adjacent glia in the ventral spinal cord. JOURNAL OF NEUROSCIENCE METHODS, v. 299, p. 8-15, APR 1 2018. (15/08297-8, 13/16134-6, 14/06892-3)

INACIO, RODRIGO FABRIZZIO; ZANON, RENATA GACIELLE; DE CASTRO, MATEUS VIDIGAL; DE SOUZA, HENRIQUE MARQUES; BAJGELMAN, MARCIO CHAIM; VERINAUD, LIANA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Astroglioma conditioned medium increases synaptic elimination and correlates with major histocompatibility complex of class I (MHC I) upregulation in PC12Cells. Neuroscience Letters, v. 634, p. 160-167, NOV 10 2016. (14/06892-3)

DE CASTRO, MATEUS VIDIGAL; RAMOS DA SILVA, MONIZE VALERIA; CHIAROTTO, GABRIELA BORTOLANCA; VOLPE, BRUNO BOSH; SANTANA, MARIA HELENA; MALHEIROS LUZO, ANGELA CRISTINA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Reflex arc recovery after spinal cord dorsal root repair with platelet rich plasma (PRP). Brain Research Bulletin, v. 152, p. 212-224, OCT 2019. (15/26206-0, 18/05006-0, 14/06892-3)

BARBIZAN, ROBERTA; CASTRO, MATEUS V.; FERREIRA, RUI SEABRA, JR.; BARRAVIERA, BENEDITO; OLIVEIRA, ALEXANDRE L. R.. Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 15, n. 11, p. 17-pg., 2014-11-01. (14/06892-3, 09/53846-9, 12/08101-8, 11/23236-4)

DE CASTRO, MATEUS VIDIGAL; BARBIZAN, ROBERTA; FERREIRA, RUI SEABRA, JR.; BARRAVIERA, BENEDITO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Direct Spinal Ventral Root Repair following Avulsion: Effectiveness of a New Heterologous Fibrin Sealant on Motoneuron Survival and Regeneration. NEURAL PLASTICITY, v. 2016, p. 16-pg., 2016-01-01. (14/06892-3, 13/04409-0)

BISCOLA, NATALIA PERUSSI; CARTAROZZI, LUCIANA POLITTI; FERREIRA JUNIOR, RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair. NEURAL PLASTICITY, v. 2016, p. 19-pg., 2016-01-01. (14/06892-3, 09/53846-9, 12/08101-8, 11/23236-4, 11/23377-7)

BERNARDES, DANIELLE; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Regular Exercise Modifies Histopathological Outcomes of Pharmacological Treatment in Experimental Autoimmune Encephalomyelitis. FRONTIERS IN NEUROLOGY, v. 9, NOV 20 2018. (14/06892-3, 15/04665-2)

SPEJO, ALINE BARROSO; TELES, CAROLINE BRANDAO; ZUCCOLI, GIULIANA DA SILVA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL). Journal of Neuroscience Research, v. 97, n. 4, p. 520-534, APR 2019. (14/12707-4, 12/22750-9, 14/12671-0, 14/06892-3)

RIBEIRO, PATRICIA; CASTRO, V, MATEUS; PEREZ, MATHEUS; CARTAROZZI, LUCIANA P.; SPEJO, ALINE B.; CHIAROTTO, GABRIELA B.; AUGUSTO, TAIZE M.; OLIVEIRA, ALEXANDRE L. R.. Toll-like receptor 4 (TLR4) influences the glial reaction in the spinal cord and the neural response to injury following peripheral nerve crush. Brain Research Bulletin, v. 155, p. 67-80, FEB 2020. (18/05006-0, 14/06892-3)

BOMBEIRO, ANDRE LUIS; NUNES PEREIRA, BRUNA TOLEDO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Granulocyte-macrophage colony-stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush. European Journal of Neuroscience, v. 48, n. 5, p. 2152-2164, SEP 2018. (14/06892-3, 16/03094-4)

NATALIA PERUSSI BISCOLA; LUCIANA POLITTI CARTAROZZI; SUZANA ULIAN-BENITEZ; ROBERTA BARBIZAN; MATEUS VIDIGAL CASTRO; ALINE BARROSO SPEJO; RUI SEABRA FERREIRA JR.; BENEDITO BARRAVIERA; ALEXANDRE LEITE RODRIGUES OLIVEIRA. Multiple uses of fibrin sealant for nervous system treatment following injury and disease. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, 2017-04-27. (13/23030-2, 11/23377-7, 12/02689-3, 12/20456-6, 14/06892-3, 14/11405-4, 11/02889-0, 13/04409-0, 12/08101-8, 09/53846-9, 12/22750-9, 12/13514-0, 10/00729-2)

HOELZ, AMANDA GARCIA; BERNARDES, DANIELLE; CARTAROZZI, LUCIANA POLITTI; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 16, p. 11-pg., 2022-08-12. (18/05006-0, 15/04665-2, 14/06892-3, 19/02714-7)

BISCOLA, NATALIA PERUSSI; CARTAROZZI, LUCIANA POLITTI; FERREIRA JUNIOR, RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair. NEURAL PLASTICITY, 2016. (12/08101-8, 14/06892-3, 11/23377-7, 11/23236-4, 09/53846-9)

CHIAROTTO, GABRIELA BORTOLANCA; CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; BISCOLA, NATALIA PERUSSI; SPEJO, ALINE BARROSO; GUBERT, FERNANDA; FRANCA JUNIOR, MARCONDES; MENDEZ-OTERO, ROSALIA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1(G93A)) of ALS. JOURNAL OF NEUROINFLAMMATION, v. 16, n. 1, NOV 14 2019. (13/16168-8, 17/02895-6, 18/05006-0, 14/06892-3)

MORREY, JOHN D.; OLIVEIRA, ALEXANDRE L. R.; WANG, HONG; ZUKOR, KATHERINE; DE CASTRO, MATEUS VIDIGAL; SIDDHARTHAN, VENKATRAMAN. Zika virus infection causes temporary paralysis in adult mice with motor neuron synaptic retraction and evidence for proximal peripheral neuropathy. SCIENTIFIC REPORTS, v. 9, DEC 20 2019. (14/06892-3)

CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; KIRCHHOFF, FRANK; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Role of MHC-I Expression on Spinal Motoneuron Survival and Glial Reactions Following Ventral Root Crush in Mice. CELLS, v. 8, n. 5, MAY 2019. (14/06892-3, 13/16134-6)

CHIAROTTO, GABRIELA BORTOLANCA; NARDO, GIOVANNI; TROLESE, MARIA CHIARA; FRANCA, JR., MARCONDES CAVALCANTE; BENDOTTI, CATERINA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. The Emerging Role of the Major Histocompatibility Complex Class I in Amyotrophic Lateral Sclerosis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 11, NOV 2017. (14/06892-3, 17/02895-6, 13/16168-8)

BISCOLA, NATALIA PERUSSI; CARTAROZZI, LUCIANA POLITTI; ULIAN-BENITEZ, SUZANA; BARBIZAN, ROBERTA; CASTRO, MATEUS VIDIGAL; SPEJO, ALINE BARROSO; FERREIRA, JR., RUI SEABRA; BARRAVIERA, BENEDITO; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Multiple uses of fibrin sealant for nervous system treatment following injury and disease. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, n. 1, MAR 14 2017. (12/20456-6, 12/08101-8, 14/06892-3, 12/22750-9, 12/02689-3, 11/23377-7, 11/02889-0, 13/04409-0, 09/53846-9, 14/11405-4, 10/00729-2, 13/23030-2, 12/13514-0)

SPEJO, A. B.; CHIAROTTO, G. B.; FERREIRA, A. D. F.; GOMES, D. A.; FERREIRA JR, R. S.; BARRAVIERA, B.; OLIVEIRA, A. L. R.. Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons by treatment with adult mesenchymal stem cells. JOURNAL OF NEUROINFLAMMATION, v. 15, AUG 14 2018. (14/06892-3, 12/22750-9, 13/16168-8)

BOMBEIRO, ANDRE LUIS; DE MELO LIMA, BRUNO HENRIQUE; BONFANTI, AMANDA PIRES; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Improved mouse sciatic nerve regeneration following lymphocyte cell therapy. Molecular Immunology, v. 121, p. 81-91, MAY 2020. (18/05006-0, 14/06892-3)

LIMA, BRUNO HENRIQUE DE MELO; BOMBEIRO, ANDRE LUIS; CARTAROZZI, LUCIANA POLITTI; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. The Time Course of MHC-I Expression in C57BL/6J and A/J Mice Correlates with the Degree of Retrograde Gliosis in the Spinal Cord following Sciatic Nerve Crush. CELLS, v. 11, n. 23, p. 20-pg., 2022-12-01. (14/06892-3, 18/05006-0)

BERNARDES, DANIELLE; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Comprehensive catwalk gait analysis in a chronic model of multiple sclerosis subjected to treadmill exercise training. BMC Neurology, v. 17, AUG 22 2017. (14/06892-3, 15/04665-2)

BOMBEIRO, ANDRE LUIS; RODRIGUES HELL, RAFAELA CHITARRA; SIMOES, GUSTAVO FERREIRA; DE CASTRO, MATEUS VIDIGAL; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro. Neuroscience Letters, v. 647, p. 97-103, APR 24 2017. (11/08123-9, 14/06892-3, 10/05370-2)

ASSAF, KYL; LEAL, CLAUDENETE VIEIRA; DERAMI, MARIANA SILVEIRA; DE REZENDE DUEK, ELIANA APARECIDA; CERAGIOLI, HELDER JOSE; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Sciatic nerve repair using poly(epsilon-caprolactone) tubular prosthesis associated with nanoparticles of carbon and graphene. BRAIN AND BEHAVIOR, v. 7, n. 8, AUG 2017. (14/06892-3)

CARTAROZZI, LUCIANA P.; SPEJO, ALINE B.; FERREIRA, JR., RUI S.; BARRAVIERA, BENEDITO; DUEK, ELIANA; CARVALHO, JULIANA L.; GOES, ALFREDO M.; OLIVEIRA, ALEXANDRE L. R.. Mesenchymal stem cells engrafted in a fibrin scaffold stimulate Schwann cell reactivity and axonal regeneration following sciatic nerve tubulization. Brain Research Bulletin, v. 112, p. 14-24, MAR 2015. (14/06892-3, 12/08101-8, 11/23236-4, 09/53846-9)

BOMBEIRO, ANDRE LUIS; NUNES PEREIRA, BRUNA TOLEDO; BONFANTI, AMANDA PIRES; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Immunomodulation by dimethyl fumarate treatment improves mouse sciatic nerve regeneration. Brain Research Bulletin, v. 160, p. 24-32, JUL 2020. (18/05006-0, 14/06892-3)

MENEZES CARVALHO, NAHANNA ZIMMERMANN; CHIAROTTO, GABRIELA BORTOLANCA; BERNARDES, DANIELLE; GELINSKI KEMPE, PAULA REGINA; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Neuroprotection by dimethyl fumarate following ventral root crush in C57BL/6J mice. Brain Research Bulletin, v. 164, p. 184-197, NOV 2020. (14/06892-3, 18/05006-0)