“…As suggested by successful MSC use in a number of pathological scenarios involving uncontrolled immune activation with consequent tissue damage, like for example H9N2 induced acute lung injury, ARDS, autoimmune diseases and graft-versus-host disease ( Waterman et al, 2010 ; Elgaz et al, 2019 ; Coelho et al, 2020 ; Yen et al, 2020 ; Barros et al, 2021 ; Musial and Gorska-Ponikowska, 2021 ; Su et al, 2021 ), the undeniable immunomodulatory and inflammation relieving properties of MSCs make them putative candidates as rejuvenating factors for the older immune system, on the basis of the documented ability to reduce pro-inflammatory mediators and to promote the expansion of regulatory lymphocyte subsets ( Yeo et al, 2021 ). Also, MSC transplantation can contribute to the amelioration of aging frailty ( Schulman et al, 2018 ; Florea et al, 2019 ; Sun et al, 2019 ), but MSC may exhibit age related deteriorating functions linked to inflammageing, especially in terms of alterations in number and characteristics of extracellular vesicles, DAMP production, excessive IL-6 release, loss of MSC ability to shift monocyte polarization toward M2, and triggering of ineffective hemopoiesis ( Tsuruhara et al, 2017 ; Lee and Yu, 2020 ).…”