TY - JOUR
T1 - Co-injection of mesenchymal stem cells with endothelial progenitor cells accelerates muscle recovery in hind limb ischemia through an endoglin-dependent mechanism
AU - Rossi, Elisa
AU - Goyard, Céline
AU - Cras, Audrey
AU - Dizier, Blandine
AU - Bacha, Nour
AU - Lokajczyk, Anna
AU - Guerin, Coralie L.
AU - Gendron, Nicolas
AU - Planquette, Benjamin
AU - Mignon, Virginie
AU - Bernabeu, Carmelo
AU - Sanchez, Olivier
AU - Smadja, David M.
N1 - Funding Information:
This work was supported by grants from Région Ile de France-CORDDIM (Domaine d’intérêt majeur Cardiovasculaire Obésité Rein Diabète) and the Conny-Maeva Charitable Foundation. Car-melo Bernabeu is supported by Ministerio de Economia y Compe-titividad of Spain (SAF2013–43421-R to C.B.). Elisa Rossi’s salary is supported by a grant from the Conny-Maeva Charitable Foundation. Nour Bacha and Celine Goyard’s salaries are supported by a grant from Fond de Dotation pour la Recherche en Santé Respi-ratoire.
Publisher Copyright:
© Schattauer 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Endoglin
KW - Endothelial cells
KW - Endothelial progenitor cells
KW - Hind limb ischemia
KW - Mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=85031111720&partnerID=8YFLogxK
U2 - 10.1160/TH17-01-0007
DO - 10.1160/TH17-01-0007
M3 - Article
C2 - 28771278
AN - SCOPUS:85031111720
SN - 0340-6245
VL - 117
SP - 1908
EP - 1918
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 10
ER -