CD10 expression identifies a subset of human perivascular progenitor cells with high proliferation and calcification potentials

Author:

Ding Lijun123ORCID,Vezzani Bianca24,Khan Nusrat2,Su Jing1,Xu Lu1,Yan Guijun1,Liu Yong5,Li Ruotian6,Gaur Anushri2,Diao Zhenyu1,Hu Yali1ORCID,Yang Zhongzhou7,Hardy W. Reef8,James Aaron W.89,Sun Haixiang110ORCID,Péault Bruno28

Affiliation:

1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China

2. MRC Center for Regenerative Medicine and Center for Cardiovascular Science, University of Edinburgh, Scotland, UK

3. Clinical Center for Stem Cell Research, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China

4. Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy

5. Department of Experimental Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China

6. Department of Cardiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China

7. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, People's Republic of China

8. Orthopedic Hospital Research Center and Broad Stem Cell Center, David Geffen School of Medicine, University of California, Los Angeles, California

9. Department of Pathology, Johns Hopkins University, Baltimore, Massachusetts

10. Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China

Abstract

Abstract The tunica adventitia ensheathes arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells express the CD10/CALLA cell surface metalloprotease. Both CD10+ and CD10− adventitial cells displayed phenotypic features of MSCs when expanded in culture. However, CD10+ adventitial cells exhibited higher proliferation, clonogenic and osteogenic potentials in comparison to their CD10− counterparts. CD10+ adventitial cells increased expression of the cell cycle protein CCND2 via ERK1/2 signaling and osteoblastogenic gene expression via NF-κB signaling. CD10 expression was upregulated in adventitial cells through sonic hedgehog-mediated GLI1 signaling. These results suggest that CD10, which marks rapidly dividing cells in other normal and malignant cell lineages, plays a role in perivascular MSC function and cell fate specification. These findings also point to a role for CD10+ perivascular cells in vascular remodeling and calcification. Significance statement Perivascular adventitial cells include multipotent progenitor cells giving rise in culture to mesenchymal stem/progenitor cells. The present data show that a subset of human adventitial cells natively express the CD10 surface marker, regulated by sonic hedgehog/GLI1 signaling. Purified CD10+ adventitial cells exhibit high proliferative, clonogenic and osteogenic potentials, suggesting a role in pathologic vascular remodeling.

Funder

Musculoskeletal Transplant Foundation

Maryland Stem Cell Research Foundation

American Cancer Society

Department of Defense

NIH/NIAMS

BIRAX Regenerative Medicine Initiative

British Heart Foundation

Jiangsu Province Social Development Project

Nanjing Medical Science Development Project

Nature Science Foundation of China

National Key Research and Development Program of China

U.S. Department of Defense

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Basic Research Program of China

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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