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 A2A 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.
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Abbreviations
- 6-OHDA:
-
2,4,5-Trihydroxyphenethylamine
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- AMP, ADP, ATP:
-
Adenosine 5′ mono-, di-, triphosphate
- Aβ:
-
Amyloid beta
- BBG:
-
Brilliant Blue G
- BM:
-
Bone marrow
- BM-MNC:
-
Bone marrow–derived mononuclear cell
- CNS:
-
Central nervous system
- COX-2:
-
Cyclooxygenase-2
- EAE:
-
Experimental autoimmune encephalomyelitis
- EC:
-
Endothelial cell
- EDSS:
-
Expanded Disability Status Scale
- ESC:
-
Embryonic stem cell
- FGF:
-
Fibroblast growth factor
- FRS:
-
Functional Rating Scale
- GABA:
-
γ-Aminobutyric acid
- GDNF:
-
Glial cell line–derived neurotrophic factor
- GFAP:
-
Glial fibrillary acidic protein
- HSC:
-
Hematopoietic stem cell
- hUC-MSC:
-
Human umbilical cord–derived mesenchymal stem cell
- IFN-γ:
-
Interferon gamma
- IL-1β/2/6/9/10/17:
-
Interleukin 1β/2/6/9/10/17
- iPSC:
-
Induced pluripotent stem cell
- MNC:
-
Mononuclear cell
- MOG:
-
Myelin oligodendrocyte glycoprotein
- MPTP:
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- MRI:
-
Magnetic resonance imaging
- MS:
-
Multiple sclerosis
- MSC:
-
Mesenchymal stem cell
- MSC-NTF:
-
MSC-secreting neurotrophic factors
- NPC:
-
Neural progenitor cell
- NSC:
-
Neural stem cell
- PD:
-
Parkinson’s disease
- PKA/C:
-
Protein kinase A/C
- PLP:
-
Proteolipid protein
- PMS:
-
Progressive multiple sclerosis
- RRMS:
-
Relapsing-remitting multiple sclerosis
- SGZ:
-
Subgranular zone
- SMC:
-
Smooth muscle cell
- SOD1-G93A:
-
Superoxide dismutase 1 mutant (glycine 93 changed to alanine)
- SOD1:
-
Superoxide dismutase 1
- Sox1-GFP ESC:
-
Sox1-green fluorescent protein embryonic stem cell
- SVZ:
-
Subventricular zone
- Tg APP/PS1:
-
Double transgenic mice expressing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9)
- Tg2576 mice:
-
Transgenic mice expressing the human amyloid precursor protein gene carrying the Swedish mutation (HuAPP695swe)
- TNF-α:
-
Tumor necrosis factor-alpha
- UDP, UTP:
-
Uridine di-, triphosphate
- VEGF:
-
Vascular endothelial growth factor
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Acknowledgments
HU acknowledges grant support from the São Paulo Research Foundation (FAPESP, Project No. 2012/50880-4 and 2018/08426-0). TG (Project No. 2015/13345-1-PD) and RA (Project No. 2019/05384-8-TT) are thankful for FAPESP fellowships. AOG thanks the National Council for Scientific and Technological Development (CNPq, Project No. 154512/2018-4). AG is grateful for CAPES-PNPD fellowship (Project No. 33002010017PO). DER thanks the support provided by the Incentive Program for attracting postdocs Attraction of the University of São Paulo, Brazil. We thank Biorender software where we made the figures.
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Andrejew, R. et al. (2019). Targeting Purinergic Signaling and Cell Therapy in Cardiovascular and Neurodegenerative Diseases. In: Ratajczak, M. (eds) Stem Cells. Advances in Experimental Medicine and Biology, vol 1201. Springer, Cham. https://doi.org/10.1007/978-3-030-31206-0_14
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