Abstract
Inflammatory bowel diseases (IBD) consisting of persistent and relapsing inflammatory processes of the intestinal mucosa are caused by genetic, environmental, and commensal microbiota factors. Despite recent advances in clinical treatments aiming to decrease inflammation, nearly 30% of patients treated with biologicals experienced drawbacks including loss of response, while others can develop severe side effects. Hence, novel effective treatments are highly needed. Mesenchymal stem/stromal cell (MSCs) therapy is an innovative therapeutic alternative currently under investigation for IBD. MSCs have the inherent capacity of modulating inflammatory immune responses as well as regenerating damaged tissues and are therefore a prime candidate to use as cell therapy in patients with IBD. At present, MSC-based therapy has been shown preclinically to modulate intestinal inflammation, whilst the safety of MSC-based therapy has been demonstrated in clinical trials. However, the successful results in preclinical studies have not been replicated in clinical trials. In this review, we will summarize the protocols used in preclinical and clinical trials and the novel approaches currently under investigation which aim to increase the beneficial effects of MSC-based therapy for IBD.
Highlights
This review provides a detailed overview of protocols and technical approaches currently under development which aim to increase the beneficial effects of Mesenchymal stem/stromal cell (MSCs)-based therapy in preclinical studies of Inflammatory bowel diseases (IBD)
As in other immune-mediated disorders, such as rheumatoid arthritis [31], several preclinical studies in IBD with MSC-based therapy have observed improved efficacy when the MSC infusion was performed during the early phases of the disease rather than at pre-onset or during chronic phases of inflammation induced by treatment with
In preclinical models of IBD, several groups have carried out experiments with MSCs deficient in different molecules aiming to further delineate additional molecular mechanisms involved in the beneficial effects of MSC-based therapy in experimental colitis such as FASL [38], tumour necrosis factor-inducible gene 6 protein (TSG-6) [20,39–42] or their extravesicles (EVs) [43], IL-1 β receptor [44], cystathionine β-synthase (Cbs) [45], Jagged-1 and TLR3 [46], autoimmune regulator (Aire) [47], insulin-like growth factor binding protein 7 (IGFBP7) [48], thrombospondin-1 (TSP-1, TGF-β activator) [49], matrix Gla-protein (MGP) [50], or CCL2 [51] (Supplementary Table S4)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. IL12 and IL23 antibodies that drive the differentiation and function of specific immune cells (ustekinumab) [5] and modulators of lymphocyte trafficking (anti–α4β7 integrin antibodies such as vedolizumab) have been approved for IBD patients [2] Together with these biological treatments, the use of hematopoietic stem cell (HSCs) transplantation has been explored in some severe forms of gastrointestinal diseases, including IBD [6]. Despite these advances, nearly 30% of patients do not respond to current treatments for IBD, and 50% of them suffer allergic reactions or become refractory over time [1,2].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
