Secretome of mesenchymal stem cells

Mesenchymal stem cells (MSCs) are a group of heterogeneous non-hematopoietic cells with self-renewal and multi-lineage differentiation potential, and have been widely used for cell-based therapies. While the mechanisms for the beneficial effects of MSCs on tissue repair and regeneration are complex and not fully understood, paracrine signaling is believed to be at least partially responsible for their therapeutic benefits. MSCs express and secret a large number of paracrine factors with a wide spectrum of biological functions including cell proliferation, differentiation, migration, anti-apoptosis, metabolism, immunomodulation, anti-inflammation, angiogenesis, and tissue remodeling. The regulation on the expression and production of the paracrine factors and related signaling molecules in MSCs are complex, and involves a variety of signaling pathways including Akt, STAT-3, p38 MAPK, and TNF receptors. The paracrine function of MSCs is closely associated with the species, age, and gender of the sources, and environmental factors like hypoxia, as well as the presence of stimuli such as tumor necrosis factor. Some disease conditions especially diabetes mellitus have significant impact on paracrine signaling of MSCs. Significant challenges remain on understanding how paracrine mechanisms work on the target tissues of MSCs, and how to design a therapeutic regimen with different paracrine factors to achieve an optimal outcome for tissue protection and regeneration.