Thromb Haemost 2017; 117(10): 1908-1918
DOI: 10.1160/TH17-01-0007
Endothelium and Angiogenesis
Schattauer GmbH

Co-injection of mesenchymal stem cells with endothelial progenitor cells accelerates muscle recovery in hind limb ischemia through an endoglin-dependent mechanism

Elisa Rossi
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
,
Céline Goyard
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
3  AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department, Paris, France
,
Audrey Cras
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
4  AP-HP, Saint Louis Hospital, Cell Therapy Department, Paris, France
,
Blandine Dizier
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
,
Nour Bacha
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
,
Anna Lokajczyk
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
,
Coralie L. Guerin
5  National Cytometry Platform, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg
,
Nicolas Gendron
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
8  AP-HP, European Georges Pompidou Hospital, Hematology Department, Paris, France
,
Benjamin Planquette
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
3  AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department, Paris, France
,
Virginie Mignon
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
6  Cellular and Molecular Imaging Facility, Inserm US 25, CNRS UMS 3612, Faculty of Pharmacy of Paris, Paris Descartes University, Paris, France
,
Carmelo Bernabeu
7  Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
,
Olivier Sanchez
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
3  AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department, Paris, France
,
David M. Smadja
1  Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2  Inserm UMR-S1140, Paris, France
8  AP-HP, European Georges Pompidou Hospital, Hematology Department, Paris, France
› Author Affiliations
Further Information

Publication History

Received: 04 January 2017

Accepted after major revision: 21 June 2017

Publication Date:
10 November 2017 (online)

Summary

Endothelial colony-forming cells (ECFCs) are progenitor cells committed to endothelial lineages and have robust vasculogenic properties. Mesenchymal stem cells (MSCs) have been described to support ECFC-mediated angiogenic processes in various matrices. However, MSC-ECFC interactions in hind limb ischemia (HLI) are largely unknown. Here we examined whether co-administration of ECFCs and MSCs bolsters vasculogenic activity in nude mice with HLI. In addition, as we have previously shown that endoglin is a key adhesion molecule, we evaluated its involvement in ECFC/MSC interaction. Foot perfusion increased on day 7 after ECFC injection and was even better at 14 days. Co-administration of MSCs significantly increased vessel density and foot perfusion on day 7 but the differences were no longer significant at day 14. Analysis of mouse and human CD31, and in situ hybridization of the human ALU sequence, showed enhanced capillary density in ECFC+MSC mice. When ECFCs were silenced for endoglin, coinjection with MSCs led to lower vessel density and foot perfusion at both 7 and 14 days (p<0.001). Endoglin silencing in ECFCs did not affect MSC differentiation into perivascular cells or other mesenchymal lineages. Endoglin silencing markedly inhibited ECFC adhesion to MSCs. Thus, MSCs, when combined with ECFCs, accelerate muscle recovery in a mouse model of hind limb ischemia, through an endoglindependent mechanism.

Supplementary Material to this article is available online at www.thrombosis-online.com.