Comparison of the regenerative potential for lung tissue of mesenchymal stromal cells from different sources/locations within the body

Abstract

To date, bone marrow-derived mesenchymal stromal cells (MSCs) have been considered the golden standard among MSC cell-based therapies. However, the harvesting of bone marrow is a highly invasive procedure and the number of MSCs isolated is low, and it declines with increasing age. MSCs with immune-regulatory and regenerative properties can be isolated from many different tissues; however, bone marrow-derived MSCs are so far the most thoroughly characterized MSC population. Despite an increased interest in using MSCs for clinical approaches in severe lung disorders, the biological function of MSCs after administration is not completely known, in particular, of MSCs extracted from other tissues than bone marrow aspirates. MSCs do not engraft after infusion, and data demonstrate that the majority of MSCs tend to be cleared from the lungs within a few days, suggesting a fast, short acting, and paracrine effect. Following activation, MSCs produce and secrete mediators, the secretome, that influence the microenvironment and the surrounding resident cells in order to modulate and repair damaged tissue. Exploring the MSC secretome has attracted much attention, and today it is known to consist of an array of molecules that is important for their regenerative and protective abilities. However, recent data suggest that the secretome profiles differ significantly depending on the MSC source, donor site, and external stimulation. In addition, the microenvironment that the infused MSCs encounter most likely plays an important role in influencing the therapeutic effect of MSCs. The composition of the microenvironment is unique in every tissue type and varies by developmental age. Changes in both stiffness and composition drastically affect MSC fate and function. The aim of this chapter is to provide a comparison of the potential of MSCs obtained from different cellular sources, and how they can be used as therapeutic agents to treat lung disorders.