“…The paradigm of regenerative medicine is based on the potential of stem cells to maintain tissue homeostasis by replacing dead cells with newly differentiated progenies and releasing active molecules having a critical role in the regenerative processes (autocrine and paracrine actions) [200,211,250,251]. These biological properties are well-maintained, even when stem cells are transplanted into a host tissue/organ in-vivo (direct transplantation) [211,252,253], or when they are engineered with a therapeutic gene (gene-therapy) [254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270], or when they are combined with biomaterials to generate an ex-vivo tissue (tissue engineering) [240,271,272,273,274,275,276,277,278,279,280,281,282,283,284,285]. A further advance is the recent organ-on-a-chip technology [286], which recapitulate the human physiology through culturing stem cells in a tailored artificial tissue or in a single organ system (e.g., cardiac or lung tissues) [278,287,288,289].…”