Inflammatory Bowel Disease
Inflammatory bowel disease (IBD for short) is a chronic inflammatory disease that mainly affects the gastrointestinal tract. Inflammation can be in a part of the gastrointestinal tract, such as the large intestine, or it can be anywhere in the digestive tract, from the mouth to the anus. Inflammatory bowel disease includes two common types Crohn's disease (CD) and ulcerative colitis (UC). There is also a small number of patients who present with dual features of Crohn's disease and ulcerative colitis, making it difficult to distinguish between Crohn's disease and ulcerative colitis, this is called indeterminate colitis.
Clinical Manifestations of Inflammatory Bowel Disease
The characteristic of ulcerative colitis is that the lesions often develop from the rectum, are limited to the colon, involve the mucosa and submucosa of the colon, show continuous inflammatory changes, involve the distal colon, and can develop retrogradely. The lesions are generally the most severe in the rectum. The most common clinical manifestations are persistent or recurrent diarrhea, mucus, purulence, and bloody stools accompanied by abdominal pain, tenesmus (that is, often wanting to defecate, but going to the bathroom to pass little or no stool), and varying degrees of systemic symptoms. The course of the disease usually lasts 4-6 months. More than a week.
The clinical manifestations of Crohn's disease are diverse, including gastrointestinal manifestations, systemic manifestations, extraintestinal manifestations, and complications. Digestive tract manifestations mainly include diarrhea and abdominal pain, which may include bloody stools. Systemic manifestations include weight loss, fever, loss of appetite, fatigue, anemia, etc. Growth retardation can be seen in adolescent patients, extraintestinal manifestations are similar to UC. Diarrhea, abdominal pain, and weight loss are common symptoms of CD. If these symptoms appear, especially in young patients, the possibility of the disease should be considered. If it is accompanied by extraintestinal manifestations and/or perianal lesions, the disease is highly suspected. Perianal abscess and perianal fistula may be the first diagnosis manifestations of a small number of CD patients and should be paid attention to.
Whether it is UC or CD, extraintestinal complications may occur, including joint pain, arthritis, recurrent oral ulcers, erythema nodosum, ankylosing spondylitis, sclerosing cholangitis, and pyoderma gangrenosum.
Stem Cells Treat Inflammatory Bowel Disease
1. Hematopoietic stem cells (HSCs) treat inflammatory bowel disease
Inflammatory bowel disease is an autoimmune disease, and hematopoietic stem cells can be isolated from peripheral blood, bone marrow, umbilical cord blood, etc., and these cells can directly migrate to damaged tissues or differentiate into epithelial cells and immune regulatory cells to restore normal mucosal tissue. In theory, hematopoietic stem cells could establish a new immune system in the intestines of IBD patients to avoid autoimmune attacks. The study found that Treg, TLR4, TNF-α, and IL-10 were higher than expected in patients with Crohn's disease before hematopoietic stem cell transplantation. After the transplantation of hematopoietic stem cells, the above cells and cytokines were significantly reduced, suggesting that hematopoietic stem cells have immune regulation, and can reduce the patient's inflammatory response.
2. Mesenchymal stem cells (MSCs) treat inflammatory bowel disease
Mesenchymal stem cells are multipotent adult stem cells derived from ectoderm and mesoderm and can be derived from bone marrow, adipose, and other tissues. Studies have found that mesenchymal stem cells achieve the purpose of treating inflammatory bowel disease mainly through mechanisms such as local microcirculation construction, colonization and repair, and immune regulation.
The Mechanism of Stem Cell Treatment for IBD
1. Regulating the immune system
Hematopoietic stem cell transplantation (HSCT) induces the differentiation of various types of immune cells, while mesenchymal stem cell transplantation (MSCT) mainly regulates immune cells by secreting cytokines or vesicles. For IBD patients, MSCs mainly regulate immune cells in the gut by secreting hormones or vesicles. They regulate the polarization of macrophages to the M2 phenotype, inhibit the proliferation of Th1 and Th17 helper T cells, promote the differentiation of regulatory T cells, and inhibit the maturation and differentiation of DCs, ultimately suppressing inflammation.
2. Repair of intestinal mucosal barrier
Patients with inflammatory bowel disease have abnormal intestinal mucosal barrier function, leading to increased mucosal permeability and intestinal mucosal barrier destruction. Mesenchymal stem cells have the ability to release cytokines or chemokines, which can not only stimulate the proliferation of intestinal epithelial cells but also promote the endogenous repair of IBD intestinal epithelial cells and inhibit apoptosis, so as to achieve the purpose of curing the disease.
3. Improve intestinal microecology
In patients with inflammatory bowel disease, chronic inflammation of the colon is affected by microvascular dysfunction and endothelial barrier damage, which can lead to persistent hypoperfusion and poor healing of colonic tissue. Mesenchymal stem cells mainly play a role in tissue repair by differentiating into vascular endothelial cells (ECs), promoting angiogenesis, and improving local blood supply.
4. Promote angiogenesis
Microvascular dysfunction and endothelial barrier damage occur in IBD, which can affect colonic tissue perfusion and healing. MSCs secrete various angiogenic factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), and angiopoietin-1, that promote EC proliferation and the formation of new blood vessels. In addition, MSCs can differentiate into vascular endothelial cells and promote angiogenesis.
Mechanistically, stem cells act on IBD lesions by regulating immune cells and repairing the intestinal mucosal barrier, which directly combats chronic intestinal inflammation. In addition, stem cells can also play a beneficial role in enhancing intestinal microecology, solving microcirculation disorders, and preventing fibrosis and cancer.
References
- Yue N.; et al. Application of nanoparticles in the diagnosis of gastrointestinal diseases: a complete future perspective. International Journal of Nanomedicine. 2023: 4143-4170.
- Reider S.; et al. Hematopoietic stem cell transplantation in refractory Crohn's disease: should it be considered? Cells. 2022, 11(21): 3463.
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