Targeting Purinergic Signaling and Cell Therapy in Cardiovascular and Neurodegenerative Diseases

Author(s)

Andrejew, Roberta ; Glaser, Talita ; Oliveira-Giacomelli, Agatha ; Ribeiro, Deidiane ; Godoy, Mariana ; Granato, Alessandro ; Ulrich, Henning ; Ratajczak, MZ

• Document type: Journal article
• Source: STEM CELLS: THERAPEUTIC APPLICATIONS; v. 1201, p. 79-pg., 2019-01-01.

Abstract

Extracellular purines exert several functions in physiological and -pathophysiological mechanisms. ATP acts through P2 receptors as a neurotransmitter and neuromodulator and modulates heart contractility, while adenosine participates in neurotransmission, blood pressure, and many other mechanisms. Because of their capability to differentiate into mature cell types, they provide a unique therapeutic strategy for regenerating damaged tissue, such as in cardiovascular and neurodegenerative diseases. Purinergic signaling is pivotal for controlling stem cell differentiation and phenotype determination. Proliferation, differentiation, and apoptosis of stem cells of various origins are regulated by purinergic receptors. In this chapter, we selected neurodegenerative and cardiovascular diseases with clinical trials using cell therapy and purinergic receptor targeting. We discuss these approaches as therapeutic alternatives to neurodegenerative and cardiovascular diseases. For instance, promising results were demonstrated in the utilization of mesenchymal stem cells and bone marrow mononuclear cells in vascular regeneration. Regarding neurodegenerative diseases, in general, P2X7 and A(2A) receptors mostly worsen the degenerative state. Stem cell-based therapy, mainly through mesenchymal and hematopoietic stem cells, showed promising results in improving symptoms caused by neurodegeneration. We propose that purinergic receptor activity regulation combined with stem cells could enhance proliferative and differentiation rates as well as cell engraftment. (AU)

• FAPESP's process: 18/08426-0 - Indole alkaloid sub products of Maqui (Aristotelia chilensis) processing as food additives to Alzheimer's Disease treatment
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/05384-8 - Role of Bradykinin in Neuroblastoma Metastasis
• Grantee: Roberta Andrejew Caetano
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 15/13345-1 - Huntington's disease: Huntingtin roles during cell fate decision
• Grantee: Talita Glaser
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants