Study of the effect of intrathecal stem cells administration on a rat model of diabetic peripheral neropathy

• Grant number: 14/21962-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2015
• Effective date (End): July 29, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Carlos Amilcar Parada
• Grantee: Jalile Garcia Schiavuzzo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 17/26625-8 - The influence of mesenchymal stem cells on the electrical activity of DRG neurons in experimental diabetic neuropathy, BE.EP.DR

Abstract

Diabetic Neuropathy (DN) manifests in 60% of diabetic patients and is one of the major causes of limb amputation. Among neuropathic pain, diabetic neuropathy accounts for 30% of the cases. Although morphological and electrophysiological aspects of DN are well studied, little is known about its development and progression, difficulting effective therapies. Recently, studies are demonstrating a close correlation between diabetic neuropathy development and increase of cytokines in the Dorsal Root Ganglia (DRG). Generally, increase of pro-inflammatory cytokines is observed in inflammatory processes in the DRG, by increase of polymorphonuclear cells, for instance. In fact, our group has showed that inflammatory hyperalgesia in peripheral tissue induce increase of pro-inflammatory in the DRG, such as IL-1², without inflammatory infiltrate in the tissue. Studies involving neuropathic pain of non-diabetic origin, suggest that IL-1² released in the DRG might be an important signaling molecule between neuronal cells and satellite cells, intermediating hyperalgesia development. On the other hand, the benefic effect of mesenchymal stem cells (MST) are being demonstrated in several animal models of neuropathic pain. Although it's not known the mechanisms of anti-hyperalgesic effect of MST treatment, they seem to be enrolled in opposite to hyperalgesia development, but not in the pathology reversion. There are still few studies concerning the mechanisms enrolled in the MST anti-hyperalgesic effect in diabetic neuropathies, but some suggest that it might be related to increase of neurotrophic factors induced by administration of these cells throughout the nerve. This way, the objective of this study is to initially confirm the anti-hyperalgesic effect of MST in rats presenting diabetic neuropathy induced by sistemic administration of multiple low-doses of streptozotocin. After that, we will verify if the anti-hyperalgesic effect of MST is correlated with decrease of pro-inflammatory cytokines, such as IL-1 ² and IL-6, as well as increase of anti-inflammatory cytokines, such as IL-4 and IL-10 in the DRG. Also, since IL-1 ² and IL-6 increase expression of P2X7 receptor, we will verify if MST treatment alters the expression of this receptor in satellite-cell of DRG. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SCHIAVUZZO, Jalile Garcia. The effect of treatment with mesenchymal stem cell in hypergalgesia in experimental model of diabetic neuropathy. 0000. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.