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Scleroderma Mesenchymal Stem Cells display a different phenotype from healthy controls; implications for regenerative medicine

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Abstract

Introduction

Vascular involvement is a key feature of Systemic sclerosis (SSc). Although the pericytes/endothelial cells (ECs) cross-talk regulates vessels formation, no evidences about the pericytes contribution to ineffective angiogenesis in SSc are available. Recent findings showed similarities between pericytes and Bone Marrow Mesenchymal Stem Cells (BM-MSCs). Due to difficulties in pericytes isolation, this work explores the possibility to use BM-MSCs as pericytes surrogate, clarifying their role in supporting neo-angiogenesis during SSc.

Methods

To demonstrate their potential to normally differentiate into pericytes, both SSc and healthy controls (HC) BM-MSCs were treated with TGF-β and PDGF-BB. The expression of pericytes specific markers (α-SMA, NG2, RGS5 and desmin) was assessed by qPCR, western blot, and immunofluorescence; chemioinvasion and capillary morphogenesis were also performed. Cell-sorting of BM-MSCs co-cultured with HC-ECs was used to identify a possible change in contractile proteins genes expression.

Results

We showed that BM-MSCs isolated from SSc patients displayed an up-regulation of α-SMA and SM22α genes and a reduced proliferative activity. Moreover during SSc, both TGF-β and PDGF-BB can specifically modulate BM-MSCs toward pericytes. TGF-β was found interfering with the PDGF-BB effects. Using BM-MSCs/MVECs co-culture system we observed that SSc BM-MSCs improve ECs tube formation in stressed condition, and BM-MSCs, sorted after co-culture, showed a reduced α-SMA and SM22α gene expression.

Conclusions

BM-MSCs from SSc patients behave as pericytes. They display a more mature and myofibroblast-like phenotype, probably related to microenvironmental cues operating during the disease. After their co-culture with HC-MVECs, SSc BM-MSCs underwent to a phenotypic modulation which re-programs these cells toward a pro-angiogenic behaviour.

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Acknowledgments

This work was supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. The authors thank Prof Patricia D’Amore and Dr Tony E. Walshe for their technical assistance in 3D co-culture systems, Dr Maria Paola Nanni Costa and Dr Samuele Di Giovanni for their contribution in BM aspiration.

Ethical standards

The experiments comply with the current laws of Italy.

Conflict of interest

The authors disclose no conflict of interest.

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Authors and Affiliations

  1. Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100, L’Aquila, Italy

    Paola Cipriani, Alessandra Marrelli, Paola Di Benedetto, Vasiliki Liakouli, Francesco Carubbi, Piero Ruscitti, Saverio Alvaro, Ilenia Pantano & Roberto Giacomelli

  2. Department of Molecular Medicine, School of Medicine ‘Sapienza’ University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy

    Antonio Francesco Campese, Paola Grazioli & Isabella Screpanti

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  1. Paola Cipriani
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Correspondence to Paola Cipriani.

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Cipriani, P., Marrelli, A., Benedetto, P.D. et al. Scleroderma Mesenchymal Stem Cells display a different phenotype from healthy controls; implications for regenerative medicine. Angiogenesis 16, 595–607 (2013). https://doi.org/10.1007/s10456-013-9338-9

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