Muse cells and aortic aneurysm

The aorta is a well-organized, multilayered structure comprising several cell types, namely, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and fibroblasts, as well as an extracellular matrix (ECM), which includes elastic and collagen fibers. Aortic aneurysms (AAs) are defined as progressive enlargements of the aorta that carries an incremental risk of rupture as the diameter increases over time. The destruction of the aortic wall tissue is triggered by atherosclerosis, inflammation, and oxidative stress, leading to the activation of matrix metalloproteinases (MMPs), and inflammatory cytokines and chemokines, resulting in the loss of the structural back bone of VSMCs, ECM, and ECs. To date, cell-based therapy has been applied to animal models using several types of cells, such as VSMCs, ECs, and mesenchymal stem cells (MSCs). Although these cells indeed deliver beneficial outcomes for AAs, particularly by paracrine and immunomodulatory effects, the attenuation of aneurysmal dilation with a robust tissue repair is insufficient. Meanwhile, multilineage-differentiating stress-enduring (Muse) cells are known to be endogenous non-tumorigenic pluripotent-like stem cells that are included as several percent of MSCs. Since Muse cells are pluripotent-like, they have the ability to differentiate into cells representative of all three germ layers from a single cell and to self-renew. Moreover, Muse cells are able to home to the site of damage following simple intravenous injection and repair the tissue by replenishing new functional cells through spontaneous differentiation into tissue-compatible cells. Given these unique properties, Muse cells are expected to provide an efficient therapeutic efficacy for AA by simple intravenous injection. In this chapter, we summarize several studies on Muse cell therapy for AA including our recent data, in comparison with other kinds of cell therapies.