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

Elisa Rossi; Céline Goyard; Audrey Cras; Blandine Dizier; Nour Bacha; Anna Lokajczyk; Coralie L. Guerin; Nicolas Gendron; Benjamin Planquette; Virginie Mignon; Carmelo Bernabeu; Olivier Sanchez; David M. Smadja

doi:10.1160/TH17-01-0007

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

Autor*innen

Elisa Rossi

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France
Céline Goyard

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France

³AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department, Paris, France
Audrey Cras

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France

⁴AP-HP, Saint Louis Hospital, Cell Therapy Department, Paris, France
Blandine Dizier

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France
Nour Bacha

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France
Anna Lokajczyk

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France
Coralie L. Guerin

⁵National Cytometry Platform, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg
Nicolas Gendron

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France

⁸AP-HP, European Georges Pompidou Hospital, Hematology Department, Paris, France
Benjamin Planquette

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France

³AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department, Paris, France
Virginie Mignon

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

⁶Cellular and Molecular Imaging Facility, Inserm US 25, CNRS UMS 3612, Faculty of Pharmacy of Paris, Paris Descartes University, Paris, France
Carmelo Bernabeu

⁷Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
Olivier Sanchez

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France

³AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department, Paris, France
David M. Smadja

¹Université Paris Descartes, Sorbonne Paris Cité, Paris, France

²Inserm UMR-S1140, Paris, France

⁸AP-HP, European Georges Pompidou Hospital, Hematology Department, Paris, France

Abstract

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.

Keywords

Endothelial cells - endothelial progenitor cells - hind limb ischemia - mesenchymal stem cells - endoglin

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Referenzen

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