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

Yu Zhang,Edda Tobiasch,Andreas Pansky,Matthias Ulrich Kassack,Patrick Babczyk

doi:10.3390/ijms21176210

Abstract

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.

Highlights

Cardiovascular diseases are responsible for the majority of deaths in industrialized countries
When it was used to differentiate Human mesenchymal stem cells (hMSCs)-derived smooth muscle cells, it enhanced the percentage of calponin positive cells post-differentiation (Figure 5E). These findings suggest that the release of endogenous nucleotides from hMSC during differentiation plays a pivotal role in the regulation of endothelial and smooth muscle cell differentiation
The MSCs derived from adipose tissue constitute a more attractive cell source than MSCs derived from other regions

Summary

Introduction

Cardiovascular diseases are responsible for the majority of deaths in industrialized countries. Liposuction material is regarded as an excellent hMSC source since it can be harvested from patients in large quantities and without inflicting significant pain [10] These cells have the capacity to differentiate along multiple cell lineages into numerous cell types. 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. 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. 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

Methods

Results

Conclusion