Colon-targeted EMSCs conditional medium hydrogel for treatment of ulcerative colitis in mice.

Oral ecto-mesenchymal stem cells-conditional medium (EMSCs-CM) is a promising strategy for treating ulcerative colitis (UC). However, this therapy is currently limited by the harsh gastrointestinal environment and poor colonic targeting ability. Herein, a glutamine transaminase 2 (TG2) crosslinked EMSCs-CM hydrogel (EMSCs-CM-Gel) was fabricated by combining EMSCs-CM with negatively chargedγ-polyglutamic acid (γ-PGA) hydrogel. Intestinal epithelial cell 6 (IEC-6) was applied to construct a cell model with lipopolysaccharide to evaluate the anti-inflammatory potential of EMSCs-CMin vitro. The crosslinked gel was orally administered to mice in liquid form to access the effects of EMSCs-CM-Gelin vivo. This study was based on the fact that the hydrogel containing EMSCs-CM has negative charges, which ensure it remains at the positively charged inflamed colon tissue. The EMSCs-CM could continuously be released in the damaged colon mucosa along with the degradation of theγ-PGA hydrogel. Immunofluorescence and western blot were performed to assess the effects of EMSCs-CM-Gel on mice. The resultsin vivoshowed that EMSCs-CM-Gel could significantly suppress the expression of inflammatory cytokines, prevent the shortening of the length of the intestine and repair the intestinal barrier. Collectively, our findings provided a novel colon-targeted strategy, hoping to benefit UC patients a lot.

Olfactory mucosa tissue-derived mesenchymal stem cells lysate ameliorates LPS-induced acute liver injury in mice.

BACKGROUND: Acute liver injury (ALI) induced by sepsis seriously endangers the health of human beings every year. Mesenchymal stem cells (MSCs) lysate containing various regulators had a positive effect on anti-inflammation, hoping to provide a promising strategy in ALI. METHODS: Olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) were extracted and identified. The collected OM-MSCs were prepared after repeated freeze-thaw in phosphate buffer solution (PBS). Then, OM-MSCs lysate was filtered for future experiments. To understand the composes of OM-MSCs clearly, we detected the components of OM-MSCs lysate by western blotting. In vitro, OM-MSCs lysate was applied to evaluate the effects on normal human liver cells (LO-2) under stimulation of LPS. Lipopolysaccharide (LPS) was also injected intraperitoneally to build ALI model in mice. We further assessed the anti-inflammatory capacity of OM-MSCs lysate on ALI in vivo by aminotransferase determination, pathology observation, and immunohistochemical staining. Moreover, the immunoblot technique was performed to recognize the changes in inflammatory factors and related proteins. RESULTS: In this study, we found that OM-MSCs lysate could protect structure effectively, improve the plasma aminotransferases, diminish inflammation by releasing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß). A significant decrease in tumor necrosis factor-α (TNF-α) also occurred under the treatment of OM-MSCs lysate. In addition, trophic factors originating from OM-MSCs lysate provided a supportive micro-environment for liver recovery. Especially, up-expression of vascular endothelial growth factor (VEGF) in vivo revealed that OM-MSCs might have a great potential for healing. CONCLUSIONS: Our results demonstrated that OM-MSCs lysate could alleviate LPS-induced ALI via decreasing inflammatory cytokines and promoting recovery.