Intraluminally injected MSC spheroids at least partially attenuate experimental colitis, with fewer phagocytes and proinflammmatory cytokines, when a high dose of MSCs in spheroids was administered.
A frequent manifestation of Crohn's disease (CD) is the formation of perianal fistulas which can greatly affect patient's quality of life due to continuous pain, abscess formation and malodourous... Show moreA frequent manifestation of Crohn's disease (CD) is the formation of perianal fistulas which can greatly affect patient's quality of life due to continuous pain, abscess formation and malodourous discharge from the fistula causing skin irritation. Nowadays, a wide range of medical and surgical therapies for perianal fistulizing CD is available. However, achieving complete fistula healing is often a long process preceded by multiple relapses during the treatment. Currently, mesenchymal stromal cells (MSCs) have gained much interest as a potential therapeutic option for inflammatory disorders, including fistulizing CD, because they possess immunosuppressive and tissue regenerative properties. We performed a clinical trial evaluating MSCs as a treatment for perianal fistulas. Local administration of MSCs additional to a standardized surgical treatment was safe and feasible and resulted in a higher percentage of healed fistulas compared to placebo. In addition, several experimental studies were performed to unravel the mechanism of action of MSCs. The role of the time of MSC administration, disease severity, prestimulation of MSCs with inflammatory cytokines, migration of MSCs and the formation of spheroid-like structures are described in this thesis. Show less
