The Characteristics and Survival Potential Under Sub-lethal Stress of Mesenchymal Stromal/Stem Cells Isolated from the Human Vascular Wall

Abstract

Mesenchymal stromal/stem cells (MSCs) have been identified in multiple human tissues, including the vascular wall. High proliferative potential, multilineage, and immunomodulatory properties make vascular MSCs promising candidates for regenerative medicine. Indeed, their location is strategic for controlling vascular and extra-vascular tissue homeostasis. However, the clinical application of MSCs, and in particular vascular MSCs, is still challenging. Current studies are focused on developing strategies to improve MSC therapeutic applications, like priming MSCs with stress conditions (hypoxia, nutrient deprivation) to achieve a higher therapeutic potential. The goal of the present study is to review the main findings regarding the MSCs isolated from the human vascular wall. Further, the main priming strategies tested on MSCs from different sources are reported, together with the experience on vascular MSCs isolated from healthy cryopreserved and pathological arteries. Stress induction can be a priming approach able to improve MSC effectiveness through several mechanisms that are discussed in this review. Nevertheless, these issues have not been completely explored in vascular MSCs and potential side effects need to be investigated.

Keywords: human vascular wall; mesenchymal stromal/stem cells; sub-lethal stress; survival.

The vascular wall represents a reservoir of mesenchymal stromal/stem cells (MSCs). The exposure to stressful conditions in vitro can improve MSC therapeutic performance, for successful clinical use. These strategies can be applied to select and identify MSCs. This figure was created adapting Servier Medical Art templates (licensed under Creative Commons Attribution 3.0 Unported License smart.servier.com).

Figure 1.

Features of vascular MSCs isolated from pathological and healthy arteries. Summary of the characteristics of vascular MSCs isolated both from disease and healthy context. (A) Characterization and features of MSCs isolated from disease setting and exposed to sub-lethal stress induced by: nutrient and oxygen deprivation, and low temperature. (B) Characterization and features of MSCs isolated from human post-mortem arteries cryopreserved over than 5 years in liquid nitrogen. (C) Characterization of long-term organ culture performed on human fresh femoral arteries. Abbreviations: AAA-MSCs, abdominal aortic aneurysm-mesenchymal stem cells; hVW-MSCs, human vascular wall-mesenchymal stromal/stem cells; CoCl₂, cobalt chloride; EC, endothelial cells; I, intima tunica; M, media tunica; Adv, adventitia tunica.