Are bone marrow-derived mesenchymal stem cells the key to treating Crohn’s disease?
Researchers have demonstrated that human mesenchymal stem cells (hMSCs) can promote healing and tissue regeneration in a mouse model of Crohn’s disease.
Crohn’s disease is a chronic condition characterized by inflammation and damage to tissues in the gastrointestinal tract. Current therapeutic options include the use of immunomodulators, anti-inflammatory medication and antibody therapies. Despite this, an unmet clinical need to improve the longevity and efficacy of treatment remains.
Seeking to identify a novel approach, a team of researchers from the University of California, Davis Health (CA, US) investigated the regenerative and immunosuppressive properties of bone marrow-derived hMSCs for the treatment of Crohn’s disease.
Utilizing a mouse model of Crohn’s disease-like ileitis known as SAMP-1/YitFc, the team found that the hMSCs facilitated healing of the intestinal lining and promoted a positive immunologic response following intraperitoneal administration. The hMSCs were detected in the peritoneum cavity of the mice up to 9 days post-administration, exhibiting a histological and immunological response. Whilst they did not detect the presence of viable hMSCs by day 28, the team observed a positive histological, immunological, radiological and mucosal response in the mice.
Interestingly, the team found that most of the cells did not migrate to the small intestine but mediated their regenerative and immunosuppressive effects through the modulation of immune cells (T cells and macrophages) in the mesenteric lymph nodes. These findings are consistent with previous studies that have demonstrated limited homing of MSCs to the intestine following intraperitoneal administration.
Exploring the mechanism of action in which hMSCs promote tissue healing, the team found that paracrine factors such as prostaglandins E2 (PGE2) play an integral role in the process. PGE2 is secreted from the hMSCs into the peritoneal cavity and lymphatic vessel. The paracrine factor inhibits T cell proliferation and converts macrophages into an anti-inflammatory state. This initiates a process of efferocytosis in which apoptotic hMSCs are consumed by the macrophages, reprogramming them into an anti-inflammatory state that ultimately mediates the long-term efficacy of the therapy by reducing inflammation.
“Our findings show that MSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation, and despite being short-lived, they exert long-term effects via sustained anti-inflammatory programming of macrophages,” concluded Maneesh Dave, principal investigator of the study.
With promising findings reported in the study, the researchers are now looking to see how this approach can be clinically translated into treating patients with perianal fistulas, a condition associated with Crohn’s disease.
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