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P2 Receptors Influence hMSCs Differentiation towards Endothelial Cell and Smooth Muscle Cell Lineages

  • 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: 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: 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.

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Document Type:Article
Author:Yu Zhang, Patrick Babczyk, Andreas Pansky, Matthias Ulrich Kassack, Edda Tobiasch
Parent Title (English):International Journal of Molecular Sciences
Article Number:6210
Number of pages:17
Place of publication:Basel
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2020/08/27
Copyright:©2020 by the authors. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Funding Information:This work was supported by Bundesministerium für Bildung und Forschung (BMBF)-FHprofUnt, [FKZ: 03FH012PB2 to E.T.]; NRW FH-Extra, [FKZ: z1112fh012 to E.T.]; DAAD PPP Vigoni, [FKZ: 54669218 to E.T.]; BMBF-AIF, [FKZ: 1720 × 06 to E.T.]; Fachhochschulen NRW 2008 Geräteprogramm to E.T.; Y.Z. received the fellowship from China Scholarship Council, [No. 20100602024] and participated in the Helmholtz Space Life Sciences Research School (SpaceLife). SpaceLife is funded in equal parts by the Helmholtz Association and the German Aerospace Center (DLR).
Keyword:endothelial cell differentiation; mesenchymal stem cell; purinergic receptor; smooth muscle cell differentiation
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Projects:MeMoAthero - FHprofUnt2012: Mechanismus und Modell der Atherosklerose: Entwicklung eines Medikamententestsystems für einen neuartigen Behandlungsansatz (DE/BMBF/03FH012PB2,13FH012PB2)
Untersuchung des Einflusses ausdifferenzierender Adipozyten bei der Pathogenese des Diabetes mellitus Typ 2 (AdiPaD) (DE/BMBF/1720X06;1320X06)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Open access funding:Hochschule Bonn-Rhein-Sieg / Graduierteninstitut
Entry in this database:2020/08/28
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International