Study of the protective effect on damaged intestinal epithelial cells of rat multilineage-differentiating
Dong Sun1, Liu Yang1,2, Huan Cao1,3
1Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, 300070, P.R. China.
Abstract:
In this study, we determined whether multilineage-differentiating stress-enduring (Muse) cells exist in rat bone marrow and elucidated their effects on protection against the injury of intestinal epithelial cells associated with inflammation. Rat Muse cells were separated from bone marrow mesenchymal stem cells (BMMSCs) by trypsin-incubation stress. The group of cells maintained the characteristics of BMMSCs; however, there were high positive expression levels of stage-specific embryonic antigen-3 (SSEA-3; 75.6 ± 2.8%) and stage-specific embryonic antigen-1 (SSEA-1; 74.8 ± 3.1%), as well as specific antigens including Nanog, POU class 5 homeobox 1 (OCT 3/4), and SRY-box 2 (SOX 2). After inducing differentiation, α-fetoprotein (endodermal), α-smooth muscle actin and neurofilament medium polypeptide (ectodermal) were positive in Muse cells. Injuries of intestinal epithelial crypt cell-6 (IEC-6) and colorectal adenocarcinoma 2 (Caco-2) cells as models were induced by tumor necrosis factor-α stimulation in vitro. Muse cells exhibited significant protective effects on the proliferation and intestinal barrier structure, the underlying mechanisms of which were related to reduced levels of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and the restoration of transforming growth factor-β (TGF-β) and IL-10 in the inflammation microenvironment. In summary, there were minimal levels of pluripotent stem cells in rat bone marrow, which exhibit similar properties to human Muse cells. Rat Muse cells could provide protection against damage to intestinal epithelial cells depending on their anti-inflammatory and immune regulatory functionality. Their functional impact was more obvious than that of BMMSCs.
Insights
Multilineage-differentiating stress-enduring (Muse) cells were identified in rat bone marrow. These cells protect intestinal epithelial cells from inflammation by regulating immune responses and reducing inflammatory markers.
Area of Science:
- Stem Cell Biology
- Gastroenterology
- Immunology
Background:
- Multilineage-differentiating stress-enduring (Muse) cells are a unique type of pluripotent stem cell.
- Their presence and function in rat bone marrow remain largely uncharacterized.
- Bone marrow mesenchymal stem cells (BMMSCs) are known for their regenerative potential.
Purpose of the Study:
- To determine the existence of Muse cells in rat bone marrow.
- To characterize their properties and compare them to BMMSCs.
- To investigate their protective effects on intestinal epithelial cells against inflammation.
Main Methods:
- Rat bone marrow was processed to isolate Muse cells using trypsin-incubation stress.
- Cell surface markers (SSEA-3, SSEA-1) and pluripotency markers (Nanog, OCT 3/4, SOX 2) were analyzed.
- Differentiation potential was assessed.
- Intestinal epithelial cell lines (IEC-6, Caco-2) were injured in vitro using tumor necrosis factor-α.
- The effects of Muse cells on cell proliferation, barrier structure, and inflammatory cytokine levels (IL-6, IFN-γ, TGF-β, IL-10) were evaluated.
Main Results:
- Rat bone marrow contains minimal levels of Muse cells with characteristics similar to human Muse cells.
- These cells expressed high levels of SSEA-3, SSEA-1, Nanog, OCT 3/4, and SOX 2.
- Muse cells demonstrated significant protection of intestinal epithelial cells against TNF-α-induced injury.
- Protection was mediated by reduced IL-6 and IFN-γ, and restored TGF-β and IL-10 levels.
- Muse cells showed a more pronounced functional impact than BMMSCs.
Conclusions:
- Rat bone marrow harbors Muse cells with pluripotent stem cell properties.
- Rat Muse cells possess significant anti-inflammatory and immune regulatory functions.
- These cells offer protection against intestinal epithelial cell injury, surpassing the efficacy of BMMSCs.
Related Concept Videos
01:23Renewal of Intestinal Stem Cells
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...