Stem Cells. 2018 Feb 27. doi: 10.1002/stem.2814. [Epub ahead of print]

Identification of Adult Mesodermal Progenitor Cells and Hierarchy in Atherosclerotic Vascular Calcification.

Cho HJ¹, Lee JW^2,3, Cho HJ^2,3, Lee CS^2,3,4, Kim HS^1,2,3,4.

Abstract

The nature of calcifying progenitor cells remains elusive. In this study, we investigated the developmental hierarchy and dynamics of progenitor cells. In vitro and in vivo reconstitution assays demonstrated that Sca-1+/PDGFRα- cells in the bone marrow (BM) are the ancestors of Sca-1+/PDGFRα+ cells. Cells of CD29+Sca-1+/PDGFRα- lineage in the BM showed both hematopoietic potential with osteoclastic differentiation ability as well as mesenchymal stem cell-like properties with osteoblastic differentiation potential. Clonally-isolated BM-derived artery-infiltrated Sca-1+/PDGFRα- cells maintained osteoblastic/osteoclastic bipotency but lost hematopoietic activity. In hypercholesterolemic apolipoprotein-E-deficient (Apoe-/-) mice, the mobilization from BM to peripheral circulation, followed by migration into atherosclerotic plaques of Sca-1+/PDGFRα- cells, but not Sca-1+/PDGFRα+ cells, were significantly decreased, and IL-1β and IL-5 mediated this response. Here, we demonstrated that Sca-1+/PDGFRα- cells are mesodermal progenitor cells (MPCs) in adults, and the dynamics of progenitor cells were regulated by atherosclerosis-related humoral factors. These results may contribute to better understanding of vascular homeostasis and assist in the development of novel therapies for atherosclerosis. This article is protected by copyright. All rights reserved.