P2 Receptors Influence hMSCs Differentiation towards Endothelial Cell and Smooth Muscle Cell Lineages.
Cell Culture Techniques
Cell Differentiation
Cells, Cultured
Endothelial Cells
/ cytology
Female
Gene Expression Regulation
Humans
Lipectomy
Mesenchymal Stem Cells
/ cytology
Myocytes, Smooth Muscle
/ cytology
Purinergic P2 Receptor Agonists
/ pharmacology
Purinergic P2 Receptor Antagonists
/ pharmacology
Receptors, Purinergic P2
/ genetics
Receptors, Purinergic P2Y1
/ genetics
Young Adult
endothelial cell differentiation
mesenchymal stem cell
purinergic receptor
smooth muscle cell differentiation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
27 Aug 2020
27 Aug 2020
Historique:
received:
31
07
2020
revised:
24
08
2020
accepted:
25
08
2020
entrez:
2
9
2020
pubmed:
2
9
2020
medline:
26
2
2021
Statut:
epublish
Résumé
Human mesenchymal stem cells (hMSCs) have shown their multipotential including differentiating towards endothelial and smooth muscle cell lineages, which triggers a new interest for using hMSCs as a putative source for cardiovascular regenerative medicine. Our recent publication has shown for the first time that purinergic 2 receptors are key players during hMSC differentiation towards adipocytes and osteoblasts. Purinergic 2 receptors play an important role in cardiovascular function when they bind to extracellular nucleotides. In this study, the possible functional role of purinergic 2 receptors during MSC endothelial and smooth muscle differentiation was investigated. Human MSCs were isolated from liposuction materials. Then, endothelial and smooth muscle-like cells were differentiated and characterized by specific markers via Reverse Transcriptase-PCR (RT-PCR), Western blot and immunochemical stainings. Interestingly, some purinergic 2 receptor subtypes were found to be differently regulated during these specific lineage commitments: P2Y4 and P2Y14 were involved in the early stage commitment while P2Y1 was the key player in controlling MSC differentiation towards either endothelial or smooth muscle cells. The administration of natural and artificial purinergic 2 receptor agonists and antagonists had a direct influence on these differentiations. Moreover, a feedback loop via exogenous extracellular nucleotides on these particular differentiations was shown by apyrase digest. Purinergic 2 receptors play a crucial role during the differentiation towards endothelial and smooth muscle cell lineages. Some highly selective and potent artificial purinergic 2 ligands can control hMSC differentiation, which might improve the use of adult stem cells in cardiovascular tissue engineering in the future.
Sections du résumé
BACKGROUND
BACKGROUND
Human mesenchymal stem cells (hMSCs) have shown their multipotential including differentiating towards endothelial and smooth muscle cell lineages, which triggers a new interest for using hMSCs as a putative source for cardiovascular regenerative medicine. Our recent publication has shown for the first time that purinergic 2 receptors are key players during hMSC differentiation towards adipocytes and osteoblasts. Purinergic 2 receptors play an important role in cardiovascular function when they bind to extracellular nucleotides. In this study, the possible functional role of purinergic 2 receptors during MSC endothelial and smooth muscle differentiation was investigated.
METHODS AND RESULTS
RESULTS
Human MSCs were isolated from liposuction materials. Then, endothelial and smooth muscle-like cells were differentiated and characterized by specific markers via Reverse Transcriptase-PCR (RT-PCR), Western blot and immunochemical stainings. Interestingly, some purinergic 2 receptor subtypes were found to be differently regulated during these specific lineage commitments: P2Y4 and P2Y14 were involved in the early stage commitment while P2Y1 was the key player in controlling MSC differentiation towards either endothelial or smooth muscle cells. The administration of natural and artificial purinergic 2 receptor agonists and antagonists had a direct influence on these differentiations. Moreover, a feedback loop via exogenous extracellular nucleotides on these particular differentiations was shown by apyrase digest.
CONCLUSIONS
CONCLUSIONS
Purinergic 2 receptors play a crucial role during the differentiation towards endothelial and smooth muscle cell lineages. Some highly selective and potent artificial purinergic 2 ligands can control hMSC differentiation, which might improve the use of adult stem cells in cardiovascular tissue engineering in the future.
Identifiants
pubmed: 32867347
pii: ijms21176210
doi: 10.3390/ijms21176210
pmc: PMC7503934
pii:
doi:
Substances chimiques
P2Y14 receptor, human
0
Purinergic P2 Receptor Agonists
0
Purinergic P2 Receptor Antagonists
0
Receptors, Purinergic P2
0
Receptors, Purinergic P2Y1
0
purinoceptor P2Y4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie
ID : 03FH012PB2
Organisme : NRW FH-Extra
ID : z1112fh012
Organisme : DAAD PPP Vigoni
ID : 54669218
Organisme : BMBF-AIF
ID : 1720X06
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