Stem Cells and Cell Therapies in Lung Biology and Lung Diseases

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

“…12 Finally, once isolated from host tissue, MSCs can be expanded rapidly ex vivo, which enables prompt clinical administration. 13 In view of these advantages, MSCs have become an active focus of investigation for a wide range of diseases, such as ischaemic cardiomyopathy, 14 chronic obstructive pulmonary disease, 15 acute neurological injuries, 16 graft-versus-host disease, 17 sepsis, and acute lung injury.…”

“…[19][20][21] However, with refi ned research techniques, MSC engraftment seems to be a rare event 22,23 of unclear physiological signifi cance. 13,24 A growing number of studies have shown that MSCs have immunomodulatory and anti-infl ammatory eff ects despite minimum or absent engraftment. [25][26][27][28] Consequently, research has shifted towards identifi cation of alternative pathways through which MSCs interact with host tissue, including interactions between cells, direct interactions with the host immune system, and mitochondrial transfer.…”

“…Although the behaviour of MSCs is undoubtedly aff ected by the local microenvironment, 79,81 this eff ect cannot be reliably quantifi ed and predicted. 13 Murine MSCs, although used in many preclinical models, have unique tumorigenicity and culture requirements, which raises questions about their ability to truly replicate the behaviour of human-derived MSCs. 13 Researchers also probably do not fully appreciate the inherent diff erences between MSCs cultured from diff erent donors 82 and are only beginning to appreciate how age might aff ect MSC function.…”

“…13 Murine MSCs, although used in many preclinical models, have unique tumorigenicity and culture requirements, which raises questions about their ability to truly replicate the behaviour of human-derived MSCs. 13 Researchers also probably do not fully appreciate the inherent diff erences between MSCs cultured from diff erent donors 82 and are only beginning to appreciate how age might aff ect MSC function. 83 Finally, we remain unable to answer defi nitively basic mechanistic questions, such as how MSCs have a therapeutic eff ect on non-pulmonary tissue when given intravenously.…”

“…An emphasis on the need to ensure that preparations of MSCs used in clinical trials are of a standardised and verifi able quality is at the centre of many thoughtful reviews on the subject. 13,64,79,80,87,88 This requirement is challenging because many variables, such as temperature and culture density, can all aff ect MSC phenotype. 88 Furthermore, MSCs can be cultured from multiple sites, including adipose tissue, bone marrow, and muscle.…”