Comparative Analysis between the In Vivo Biodistribution and Therapeutic Efficacy of Adipose-Derived Mesenchymal Stromal Cells Administered Intraperitoneally in Experimental Colitis

Abstract

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. The immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless of the route of administration used, the inflammation conditions and the major histocompatibility complex context. These observations raise the question of whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose-derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the “responder” mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial for achieving an optimal modulation of inflammation.

Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

“…Alternative routes of administration have been proposed, such as intranodal [ 61 ], intra-articular (IA) [ 62 , 63 , 64 , 65 , 66 ], peri-articular [ 67 ], intra-muscular [ 68 ], and subcutaneous [ 69 ], with good results. This supports the idea that MSC-based therapy is mainly mediated by systemic biological effects [ 70 , 71 , 72 ].…”

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

“…Some studies show that intraperitoneally injected MSCs disseminate to heart, lung, liver, spleen, and kidney, but do not migrate to the colon (Song et al, 2017b). However, other studies have confirmed that intraperitoneal but not intravenous MSCs could migrate to the inflammatory site of the injured colon (Castelo-Branco et al, 2012;Lee et al, 2018;Lopez-Santalla et al, 2018). Our data showed that CM-Dil-labeled UCMSC SCM and UCMSC S&XFM−CD were only transiently recruited to the injured colon and both UCMSCs exhibited low levels of recruitment and persistence in experimental colitis.…”

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

“…Because of its anti-inflammatory properties, ASC transplantation has appeared to be an effective method for treatment of inflammatory bowel diseases in animal models [103][104][105][106][107][108][109][110]. It was found that ASC administration significantly reduced the secretion of proinflammatory cytokines (tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor), and improved the clinical disease score and histological parameters in experimentally induced models of murine colitis [103][104][105][108][109][110]. The ASC infusion resulted in a decrease in both clinical inflammatory bowel disease activity index and canine chronic enteropathy clinical activity index, in a group of treated dogs.…”