The effect of treatment with mesenchymal stem cell in hypergalgesia in experimental model of diabetic neuropathy

Author(s)

Jalile Garcia Schiavuzzo

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 0000-00-00

Examining board members

Carlos Amílcar Parada; César Renato Sartori; Gisele de Castro; Luiz Alberto Ferreira Ramos; Rafael Vercelino

• Advisor: Carlos Amílcar Parada

Abstract

Peripheral diabetic neuropathy manifests in approximately 50% of diabetic patients and is among the leading causes of peripheral limb amputation. Among the diagnosed cases of neuropathic pain, 30% of them are classified as diabetic neuropathy. Although the electrophysiological and morphological aspects of diabetic neuropathic pain are known, yet the mechanisms responsible for pain and progression in this disease are poorly understood , making effective therapies unfeasible. More recently, studies have shown a close correlation between the development of diabetic neuropathy and increased cytokines in the dorsal root ganglion (DRG). In general, an increase in proinflammatory cytokines has been observed, although there is no evidence of an inflammatory process in DRG evidenced, for example, by an increase in polymorphonuclear cells. This way, our group has shown that inflammatory hyperalgesia of peripheral tissue induces an increase in DRG proinflammatory cytokines, indicating that cytokines in the nervous system may have a neuromodulatory and not necessarily inflammatory function as in peripheral tissue. Although its increase in inflammatory process may be related to sensitization of the nociceptive pathway. In fact, our work observed by the Elisa technique an increase in inflammatory cytokines (TNF-alfa, IL-1beta, IL-6 and CINC-1) in the GRD of rats with diabetic neuropathy, and that intrathecal treatment of MSCs reduced the increase approved by STZ. Some studies using mesenchymal stem cells as a treatment for diabetic neuropathy indicate increased expression of anti-inflammatory cytokines induced by the administration of MSC. Similar result was observed in our work when quantifying anti-inflammatory cytokine (IL-10). In addition, the stem cells reduce diabetic neuropathic pain by a process that is independent of peripheral nerve regeneration. We also observed through the intracellular calcium assay technique that MSC treatment can reduce diabetic neuropathic pain through homeostatic mechanisms through the activation of P2X4 expressed in MSCs. We also observed that these receptors present in MSCs are involved in BDNF release. These data indicate that intrathecal MSC treatment is a viable therapy for the control of diabetic neuropathic pain, acting on inflammatory modulation and homeostatic mechanisms involving P2X4 receptors expressed in MSCs (AU)

• FAPESP's process: 14/21962-8 - Study of the effect of intrathecal stem cells administration on a rat model of diabetic peripheral neropathy
• Grantee: Jalile Garcia Schiavuzzo
• Support Opportunities: Scholarships in Brazil - Doctorate