Author: Sun Yat-sen University Light Blue Review Expert: Affiliated Hospital of Jiangsu University Professor Li Jing Introduction Chronic inflammation has been found to mediate a variety of diseases, including aging, cardiovascular disease, cancer, diabetes, arthritis, Alzheimer's disease, lung disease, and autoimmune diseases. How to effectively manage and control chronic inflammation has become an important issue to be solved urgently in the medical field. The literature shows that mesenchymal stem cells exert anti-inflammatory effects by inhibiting the production of inflammatory mediators, promoting the production of anti-inflammatory cytokines, promoting the polarization of macrophages, inhibiting the activation of the complement system, and promoting the repair of endothelial cells, which can help the body to fight aging, cancer and control chronic diseases. In the field of medicine, inflammation is known as the "root of all diseases". Chronic inflammation is different from the common acute inflammation caused by trauma or infection in our daily life, it is more like a "hidden" "silent killer", which lurks in our body for a long time and destroys the health of the body. The occurrence of chronic inflammation is related to a variety of factors, including poor lifestyle habits, environmental pollution, stress, etc. Long-term chronic inflammation can lead to tissue damage, which in turn induces various chronic diseases that not only affect the quality of life of patients, but can also lead to serious complications and even life-threatening. Chronic inflammation has been found to mediate a variety of diseases, including cardiovascular disease, cancer, diabetes, arthritis, Alzheimer's disease, lung disease, and autoimmune diseases. Therefore, how to effectively manage and control chronic inflammation has become an important issue to be solved urgently in the medical community. Inflammation is an endogenous factor in aging, and eliminating inflammation may be a potential anti-aging strategy In 2023, an article in Nature elaborated on the association between inflammation and aging[1]. Senescence is characterized by systemic chronic inflammation with cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. 
Add ** note, no more than 140 words (optional) Factors secreted by senescent cells, known as senescence associated secretory phenotype (SASP), can promote chronic inflammation and induce senescence in normal cells. At the same time, chronic inflammation accelerates the aging of immune cells, resulting in weakened immune function and the inability to remove senescent cells and inflammatory factors, forming a vicious circle of inflammation and aging. The level of inflammation in organs such as bone marrow, liver, and lungs continues to rise, which cannot be eliminated in time, leading to organ damage and aging-related diseases. Therefore, inflammation has been recognized as an endogenous factor in aging, and eliminating inflammation may be a potential anti-aging strategy. Nature: Inflammation leads to immunosuppression, providing an environment for cancer development Studies have shown [2] that inflammation is associated with the development and malignant progression of most cancers. Targeted inflammation control is an attractive strategy for both cancer prevention and cancer**. When it comes to cancer and inflammation, it can be divided into exogenous inflammation and intrinsic inflammation. Exogenous inflammation is caused by a variety of factors, including bacterial and viral infections, autoimmune diseases, obesity, smoking, exposure to asbestos, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, inflammation that is intrinsic to cancer or that is induced by cancer can be triggered by cancer-priming mutations and can promote malignant progression through the recruitment and activation of inflammatory cells. 
*From the ref. [2] Both exogenous and endogenous inflammation can lead to immunosuppression, thus providing an environment for tumor development. In clinical trials, lifestyle changes, including a healthy diet, exercise, alcohol and smoking cessation, have been shown to be effective in improving inflammation and reducing the risk of cancer-related death. Mesenchymal stem cells control inflammation and have 5 major mechanisms of actionMesenchymal stem cells (MSCs) are a type of adult stem cells and are a stromal cell with multiple potentials, as shown in the figure below, MSCs can differentiate into a variety of cell types. Mesenchymal stem cells can be transplanted into a wide variety of people without fear of rejection because they have been shown to have the ability to prevent adverse reactions of the immune system and are an ideal "raw material" for stem cells** [3]. In recent years, more and more studies have shown that mesenchymal stem cells have unique advantages in the field of anti-inflammatory. A recent review titled "Mesenchymal Stem Stromal Cells (MSCS): Role as Guardians of Inflammatio" published in The American Society of Gene & Cell Therapy revealed the impressive potential of mesenchymal stem cells (MSCs) in the field of anti-inflammatory [4]. 
Ref. 4) The anti-inflammatory effect of MSCS is mainly manifested in the following aspects1Inhibition of the production of inflammatory mediatorsIn the inflammatory response, various inflammatory mediators such as cytokines, chemokines, and reactive oxygen species play a key role. MSCs are able to directly inhibit the production of these inflammatory mediators by secreting specific factors. For example, MSCs are able to secrete prostaglandin E2 (PGE2), a molecule with powerful anti-inflammatory effects that inhibits the production and release of multiple inflammatory mediators. 2.Promoting the production of anti-inflammatory cytokinesIn addition to inhibiting the production of inflammatory mediators, MSCS can also promote the secretion of anti-inflammatory cytokines. These cytokines, such as IL-10, TGF-, etc., have powerful anti-inflammatory and immunomodulatory effects. They are able to inhibit the activation and proliferation of inflammatory cells, promote the resolution of inflammation and the repair of tissues. 3.Macrophage-promoting polarization Macrophages are an important cell type in the inflammatory response and have a variety of functions, including phagocytosis of pathogens, release of inflammatory mediators, and more. MSCs can affect the polarization process of macrophages and promote their transformation to anti-inflammatory (M2 type). This polarization shift allows macrophages to shift from a pro-inflammatory state to an anti-inflammatory state, thereby reducing the inflammatory response. 4.Inhibition of the Complement SystemActivation The complement system is an important component of the body's immune system and is involved in the process of multiple inflammatory responses. MSCs are able to inhibit the activation of the complement system, thereby reducing complement-mediated inflammatory damage. This effect is important for the control of chronic inflammation and autoimmune diseases. 5.Promoting endothelial cell repairEndothelial cells are the primary cell type in the inner wall of blood vessels, and their integrity and function are essential for maintaining vascular homeostasis. In the inflammatory response, endothelial cells are often damaged. MSCs can promote the repair and regeneration of endothelial cells by secreting growth factors and other active molecules, thereby maintaining vascular homeostasis and reducing inflammatory responses. Taking sepsis as an example, a schematic diagram of the role of MSCS. **From Reference 4Mesenchymal stem cells: Anti-inflammatory, a new hope for chronic disease control and health managementLong-term chronic inflammation can lead to tissue damage, which in turn induces various chronic diseases. Common chronic diseases include cardiovascular and cerebrovascular diseases, cancer, diabetes, chronic respiratory diseases, and central cerebrovascular diseases include hypertension, stroke, and coronary atherosclerotic heart disease (coronary heart disease). As a lifelong disease, chronic disease is a major public health problem affecting social and economic development, and has become the most important disease burden worldwide. MSCS has a powerful anti-inflammatory mechanism, which provides new hope for a variety of chronic inflammatory and autoimmune diseases. With the in-depth study of the anti-inflammatory mechanism of MSCS, more and more cases have proved its great potential in the field of anti-inflammatory. Add ** note, no more than 140 words (optional) As early as 2014, researchers from the Stem Cell Laboratory of the University of Milan published a review of "Clinical Application of Mesenchymal Stem Cells in Chronic Diseases" [7], which shows that the use of stem cell technology to intervene in the chronic diseases and management of middle-aged and elderly people is of great significance for the disease and the improvement of quality of life. For example, rheumatoid arthritis is a chronic autoimmune disease that manifests as joint inflammation and joint damage. One study found that injecting MSCS into the joints of patients with rheumatoid arthritis significantly reduced joint pain and swelling and improved joint function. This is mainly due to the immunomodulatory and tissue repair effects of MSCS[5]. For example, for some serious immune diseases, such as graft-versus-host disease (**HD), MSCS infusions have been shown to be effective in reducing symptoms of **HD and improving patients' quality of life. MSCs reduce the production of inflammatory factors by regulating the function of immune cells, thereby alleviating the inflammatory response of **HD. In addition, against chronic inflammatory diseases of the intestines. Studies have shown that MSCs can reduce intestinal inflammation and promote intestinal healing by inhibiting the overactivation of immune cells. This provides a new way of thinking for the treatment of inflammatory bowel disease [6]. Add ** note, no more than 140 words (optional) These cases not only demonstrate the effectiveness of MSCs in the field of anti-inflammatory, but also give us more clues about their mechanism of action. However, despite the great potential of MSCs in anti-inflammatory**, their practical application still faces many challenges and unknowns. For example, how to determine the optimal dose, how to ensure the safety and efficacy of MSCs, how to develop personalized protocols for different types of inflammatory diseases, etc. In the past two decades, more and more research on mesenchymal stem cells has been carried out, and great progress has been made in understanding the key characteristics of mesenchymal stem cells. This progress provides valuable experience for the development of reasonable cell-based protocols, and mesenchymal stem cell-based protocols have played an active role in clinical research on the control of inflammation and chronic diseases, and we have reason to believe that mesenchymal stem cells, as the controllers of inflammation, are expected to provide a new anti-inflammatory strategy and health management strategy in the future. References:[1]Inflammation and aging: signaling pathways and intervention therapies inflammation in cancer prevention and therapy J, Nair AP, Iyer M, Vellingiri B, Subramaniam MD advantages of mesenchymal stem cell over the other stem cells. acta histochem. 2023 may;125(4):152041. doi: 10.1016/j.acthis.2023.152041. epub 2023 may 9. pmid: 37167794.Links: Darwin J, and Joo Youn Oh “mesenchymal stem/stromal cells (mscs): role as guardians of inflammation.” molecular therapy : the journal of the american society of gene therapy vol. 20,1 (2012): 14-20. doi:10.1038/mt.2011.211 links: Le, López JG, López Quiceno L, Barrios Arroy**e F, Halpert K, Camacho JC safety and efficacy of mesenchymal stem cells therapy in the treatment of rheumatoid arthritis disease: a systematic review and meta-analysis of clinical trials. plos one. 2023 jul 27;18(7):e0284828. doi: 10.1371/journal.pone.0284828if: 3.7 q2 . pmid: 37498842; pmcid: pmc10374120.Links: C, Nguyen TC, Lim R, Gerstenmaier A, Sievert W, Moore GT local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal crohn's disease: a phase i open label study with long-term follow up. ebiomedicine. 2023 dec;98:104879. doi: 10.1016/j.ebiom.2023.104879if: 11.1 q1 . epub 2023 dec 1. pmid: 38042747; pmcid: pmc10755113.Link: Clinical applications of mesenchymal stem cells in chronic diseases