Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease

Rafael Kramann, Claudia Goettsch, Janewit Wongboonsin, Hiroshi Iwata, Rebekka K. Schneider, Christoph Kuppe, Nadine Kaesler, Monica Chang-Panesso, Flavia G. Machado, Susannah Gratwohl, Kaushal Madhurima, Joshua D. Hutcheson, Sanjay Jain, Elena Aikawa, Benjamin D. Humphreys

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Mesenchymal stem cell (MSC)-like cells reside in the vascular wall, but their role in vascular regeneration and disease is poorly understood. Here, we show that Gli1+ cells located in the arterial adventitia are progenitors of vascular smooth muscle cells and contribute to neointima formation and repair after acute injury to the femoral artery. Genetic fate tracing indicates that adventitial Gli1+ MSC-like cells migrate into the media and neointima during athero- and arteriosclerosis in ApoE−/− mice with chronic kidney disease. Our data indicate that Gli1+ cells are a major source of osteoblast-like cells during calcification in the media and intima. Genetic ablation of Gli1+ cells before induction of kidney injury dramatically reduced the severity of vascular calcification. These findings implicate Gli1+ cells as critical adventitial progenitors in vascular remodeling after acute and during chronic injury and suggest that they may be relevant therapeutic targets for mitigation of vascular calcification.

Original languageEnglish
Pages (from-to)628-642
Number of pages15
JournalCell Stem Cell
Volume19
Issue number5
DOIs
StatePublished - Nov 3 2016

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