Myelopathic pain treatment by transplantation of neural progenitors in animal model of spinal cord injury

• Grant number: 13/12056-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: June 30, 2017
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Guilherme Alves Lepski
• Grantee: Guilherme Alves Lepski
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alexandre Fogaça Cristante ; Camila Squarzoni Dale ; Daniel Ciampi Araujo de Andrade ; José Pinhata Otoch ; Manoel Jacobsen Teixeira ; Suely Kazue Nagahashi Marie

Abstract

Spinal cord injury is an important cause of permanent disability and chronic pain, particularly in the young population. It is known that spinal cord injury causes hyper-excitability of specific neurons in the posterior horn of the spinal cord (broad spectrum neurons), which are largely responsible for the picture of severe myelopathic pain whose delayed onset occurs after lesion. Cellular therapy has been heralded as promising for the restoration of neurological deficits stemming from these injuries. However, key questions remain open, such as the ideal stem cell type with greatest neurogenic potential as well as the mechanisms responsible for neurorestoration. Numerous procedures for neuronal differentiation in vitro and in vivo preferentially produce GABA-ergic cells, which in the initial phase of maturation are excitatory but later become inhibitory. The aim of the present work was to clarify the extent to which different types of stem cell are able to generate new neurons in injured spinal cord, the type of connection which is established, and the functional repercussion of this intervention in terms of motor recovery and reversal of the chronic neuropathic pain picture which develops after injury. With regard to myelopathic pain, our focus is the hypothesis that inhibitory cells implanted into the system may inhibit pain transmission tonically. To investigate this hypothesis, we plan to use genetically immunodepressed rats which are anesthetized and submitted to thoracic laminectomy for spinal cord compression, through the use of temporary aneurysm clips (in accordance with the national and international rules governing research on animals). Subgroups of animals shall be transplanted with a culture medium, fetal neural stem cells extracted from E12 embryos of the same species, GABAergic precursors derived from telencephalic vesicles and serotoninergic precursors from ventral medulla, as well as mesenchymal stem cells from young adult animals. The animals will be assessed for behavior in terms of pain sensitivity by applying von Frey filaments and using a hot plate on a weekly basis. After three months, the test animals will be sacrificed and their spinal cords removed, immunohistochemically stained and analyzed under a laser confocal microscope. (AU)

Scientific publications

(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)

BATISTA, CHARY M.; MARIANO, ERIC D.; DALE, CAMILA S.; CRISTANTE, ALEXANDRE F.; BRITTO, LUIZ R.; OTOCH, JOSE P.; TEIXEIRA, MANOEL J.; MORGALLA, MATTHIAS; LEPSKI, GUILHERME. Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats. NEURAL REGENERATION RESEARCH, v. 14, n. 11, p. 2011-2019, NOV 2019. (15/02154-0, 13/12056-0)

BATISTA, CHARY MARQUEZ; MARIANO, ERIC DOMINGOS; ONUCHIC, FERNANDO; DALE, CAMILA SQUARZONI; DOS SANTOS, GUSTAVO BISPO; CRISTANTE, ALEXANDRE FOGACA; OTOCH, JOSE PINHATA; TEIXEIR, MANOEL JACOBSEN; MORGALLA, MATTHIAS; LEPSKI, GUILHERME. Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat. SOMATOSENSORY AND MOTOR RESEARCH, v. 36, n. 1, p. 14-23, JAN 2 2019. (15/02154-0, 13/12056-0)