Stem Cell Therapy

Following administration, MSCs travel through the bloodstream and react to inflammatory signals such as chemokines released by the damaged tissue. These chemokines create a gradient that directs MSCs toward the injury site and prompts the endothelial cells lining the blood vessels to express adhesion molecules on their surfaces. As MSCs flow by, they roll along the endothelial surface and latch on these adhesion molecules via their surface receptors like integrins. Once securely adhered, MSCs squeeze through the endothelial barrier and continue to follow the chemical signals to reach the injury site (15). Once there, MSCs adapt to the local microenvironment and differentiate into the cell types needed to repair the injury.

In addition to directly turning into specialized cell types, MSCs play their therapeutic role through paracrine signaling by secreting a wide array of bioactive molecules, including cytokines, growth factors, and extracellular vesicles containing messenger RNAs, microRNAs, and peptides. These paracrine factors modulate the local microenvironment, promoting cell survival, proliferation, and tissue regeneration. For example, MSCs release vascular endothelial growth factor (VEGF), which facilitates angiogenesis, the formation of new blood vessels essential for supplying nutrients and oxygen to damaged tissues. They also secrete antiapoptotic factors such as hepatocyte growth factor, interleukin-6 (IL-6), and miRNA-25 to enhance cell survival, and antifibrotic factors like prostaglandin E2 (PGE2) and IL-10, which help reduce fibrotic scarring (16).

Another key mechanism by which MSCs exert therapeutic effects is immunomodulation through a combination of secreted factors and direct cell-to-cell interactions. They secrete anti-inflammatory molecules such as transforming growth factor beta (TGFβ), PGE2, IL-10, and indoleamine 2,3-dioxygenase (IDO), which suppress the activity of T cells, B cells, dendritic cells, and natural killer (NK) cells. MSCs also influence the immune system through direct contact by expressing surface molecules like programmed death-ligand 1, which induces T cell apoptosis and promotes regulatory T cell development. Additionally, MSCs can shift macrophages from a proinflammatory state to an anti-inflammatory state (17). By limiting inflammation, MSCs create an immunosuppressive environment for tissue to heal and regenerate.