Endoscopic Administration of Mesenchymal Stromal Cells Reduces Inflammation in Experimental Colitis

Abstract

Endoscopic injections of MSCs and MSC spheroids in the inflamed colon attenuate DSS-induced colitis. Our data show that endoscopic injection can be a feasible and effective novel application route for MSC therapy in patients with luminal IBD.

Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis

“…However, several preclinical studies have shown that only a low percentage of implanted MSCs can home to the injured tissue and survive in vivo, suggesting that the therapeutic action is unlikely to be due to replacement of diseased tissue (Wang et al, 2016;Lopez-Santalla et al, 2017). Indeed, we (Ma et al, 2019b) and others (Barnhoorn et al, 2018;Markovic et al, 2018) have demonstrated that the immunosuppressive characteristics of MSCs provide the theoretical grounds for MSCs therapy in experimental IBD models. Recently, MSCs have also been reported to recruit macrophages to alleviate experimental colitis (Liu et al, 2015).…”

Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease

“…Therefore, we focused on local MSC therapy for luminal IBD. In pre-clinical experiments, local administration of MSCs in the inflamed bowel during endoscopy in DSS-induced colitis in mice showed attenuation of colitis, 138 and mucosal injections of colon derived MSCs were more effective in preventing ulcer development compared with intravenously injected MSCs in a colonic wound model. 139 Recently, a phase I clinical trial started in the Leiden University Medical Center [ https://www.trialregister.nl/trial/6949 ; EudraCT number: 2017-003524-75] to determine the safety of local MSC injections in the bowel of patients with refractory ulcerative proctitis.…”

“… 141 , 142 However, there are no data available yet that show that local MSC therapy works in a comparable manner, and our published data show at least the engraftment and survival of locally injected MSCs up to 6 days post-injection. 138 …”

Mesenchymal Stromal Cell–Derived Exosomes Contribute to Epithelial Regeneration in Experimental Inflammatory Bowel Disease

“…CT26 cells (250,000 or 500,000 cells/ well) were stimulated with 20 mg/mL exosomes in non-CM. After 24 hours, cells were harvested, fixated with methanol, 3…”

“…1,2 Previously, we found that local injections of bone marrow-derived MSCs alleviated experimental colitis in mice. 3 MSCs are thought to work via modulating immune responses and stimulating tissue regeneration via secreted proteins and cell-cell contacts. In addition, recent studies have indicated that MSCs also exert effects via exosomes, which are small membrane-enclosed vesicles containing proteins, DNA, and (micro) RNAs.…”