Regenerative medicine is a high-potential sector of strategic developments in medicine and health
industry. The perspective to cure diseases up to now relied on medical treatments of long duration and
limited effectiveness, and the possibility to avoid organ transplantation renders regenerative medicine
attractive. In recent years, basic and translation research held great hope for this new field with significant
progress in the modulation of stem cell commitment in vitro and providing protocols for targeted clinical
applications. In line with this approach, mesenchymal stem cells (MSCs) have been introduced as potential
therapeutic tools to correct the breakdown of musculoskeletal disorders. MSCs are able to secrete a large
number of trophic factors capable of repairing the recipient tissue through angiogenic, anti-apoptotic and
anti-fibrotic mechanisms. In this context, adipose tissue is emerging as a clinically relevant and easy to
harvest source of multipotent progenitors to develop regenerative therapies. The present review focuses
on the clinical application of MSCs, and in particular of adipose-derived stem cells, in the musculoskeletal
disorders and on the current scientific challenges. In this perspective, we discuss future developments of
an innovative system (Lipogems) for musculoskeletal regeneration, yielding a non-expanded and ready-touse
microfractured fat tissue product harbouring MSCs and pericytes within a preserved stromal vascular
niche. The Lipogems system may also pave the way for future off-the-shelf and large-scale approaches for
reconstructive procedures and regenerative medicine