Mesenchymal Stem Cells Promote Intestinal Mucosal Repair by Positively Regulating the Nrf2/Keap1/ARE Signaling...

Area of Science:

• Stem Cell Biology
• Gastroenterology
• Immunology

Background:

• Mesenchymal stem cells (MSCs) possess anti-inflammatory and immunomodulatory properties.
• Conditioned medium (CM) derived from MSCs also demonstrates therapeutic potential.
• Colitis models are crucial for studying inflammatory bowel diseases.

Purpose of the Study:

• To investigate the ameliorative effects of MSCs and CM enemas in a mouse model of colitis.
• To elucidate the underlying molecular mechanisms, particularly the role of the Nrf2 pathway.
• To compare the efficacy of MSCs versus CM in treating experimental colitis.

Main Methods:

• Dextran sodium sulfate (DSS)-induced colitis model in mice.
• Treatment groups included MSCs, CM, and MSCs with Nrf2 inhibitor (ML385).
• Histological analyses were performed to evaluate inflammation, oxidative stress, and epithelial barrier integrity.

Main Results:

• MSCs significantly inhibited inflammatory cell infiltration and proinflammatory cytokine expression.
• MSCs enhanced intestinal mucosal repair by activating the Nrf2/Keap1/ARE pathway, increasing antioxidant enzymes (HO-1, NQO-1, SOD, CAT, GSH-Px, T-AOC), and reducing oxidative stress markers (MDA).
• Blocking Nrf2 with ML385 abolished the protective effects of MSCs, while CM showed some benefits but was less effective than MSCs.

Conclusions:

• MSCs and CM effectively promote intestinal mucosal repair in experimental colitis.
• MSC-mediated therapeutic benefits are primarily achieved through the activation of the Nrf2/Keap1/ARE pathway.
• Targeting the Nrf2 pathway presents a promising therapeutic strategy for inflammatory bowel diseases.