Increasing the success rate of rotator cuff healing remains a tremendous challenge for orthopedic surgeons, which encourage the development of new biological therapies. Among many approaches, the possibility of activating resident stem cells in situ, without the need of isolating them from biopsies and successive in vitro culturing, could represent a very promising therapeutic strategy. Along this line, it has been recently demonstrated that a lipoaspirate product, such as the Lipogems® product, contains and produces growth factors that may activate resident stem cells. Recently, it has been discovered that also the human rotator cuff contains a reservoir of progenitor cells, which can be isolated and expanded in vitro.