The medical community has become familiar with the existence of mesenchymal stem cells (MSCs) since the late 19th century. MSCs have become an intriguing topic of research due to their role in modern-day therapeutics. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the ability to differentiate into mesodermal lineages such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). These are found in the bone marrow, cord blood, peripheral blood, fallopian tube, fetal liver and lung. MSCs secrete cytokines and immune receptors which regulate the microenvironment in the host tissue.
The self-renewing capacity, multilineage potential, immunomodulation and secretion of anti-inflammatory molecules make MSCs an effective tool in treating chronic diseases. Clinical studies show that MSCs have immunomodulatory and anti-inflammatory potential. It holds great promise in avoiding a negative response from a person’s immune system by suppressing alloreactive T-cell responses which allow the cells to be transplanted in a wide range of people without fear of rejection. These transplants increase the body’s natural healing abilities. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and hide themselves from the innate immune system. These properties are the reason for the uprising in the sciences of cellular therapy in the last decades.
Immunomodulatory Features of Mesenchymal Stem Cells
The ability of MSCs to differentiate into various cell types and their capability to self-renew, repair, and heal makes them attractive candidates for therapeutic use. MSCs are widely used to treat many autoimmune diseases such as Crohn’s disease, Multiple Sclerosis, Lupus, Chronic Obstructive Pulmonary Diseases (COPD), Parkinson’s Disease. MSC therapy has been shown to alleviate autoimmune disease symptoms. Patients who are transplanted with stem cells undergo long-term chemotherapy are at risk of developing tumorigenesis. Over time, the capacity for MSCs to modulate immune responses has been undeniable. MSCs exert their immunomodulatory effects by inhibiting the complement‐mediated effects of peripheral blood mononuclear cell proliferation which have the ability to interact and regulate the function of effector cells involved in the processes of primary and acquired immune response. Activated MSCs secrete cytokines that stimulate neutrophil chemotaxis and secretion of pro‐inflammatory chemokines is involved in recruitment and stimulation of phagocytic macrophage properties.
A recent study has revealed that after administering MSCs into the body, they travel to the lungs and other tissues, suppressing the inflammatory response before they are completely cleared from the body. It was found that the pieces of the MSCs had been engulfed by monocytes and macrophages. Long-term transcription changes in the cells that engulf pieces of MSCs suppress the activation and function of T cells. A combination of computational and pharmacological approaches has identified potential receptors on monocytes and macrophages that interact with the human cord tissue mesenchymal stem cells (hCT-MSCs), which block interaction with a pharmacological inhibitor. A key cytoplasmic organelle is identified in hCT-MSCs which is necessary to reprogram the monocytes and macrophages. The immunomodulatory effects of MSCs are extended after they are physically cleared. Thus hCT‐MSCs indirectly suppress the T‐cell response by directly interacting and reprogramming monocytes and macrophages via p‐bodies, which in turn suppress inflammation. This novel mechanism of MSCs has revolutionized stem cell treatment.
Although MSCs have become a promising tool in efficient future treatment strategies, there are still questions about the use of MSCs. MSCs can cause genetic instability, tumorigenesis, chromosomal aberrations. Recently, MSCs have become a novel therapeutic choice for autoimmune diseases and are of clinical interest because of their beneficial effects in autologous transplantation. The cell-based therapeutic strategy using macrophages have long-term effects in suppressing inflammation. MSC therapy exemplifies a materializing style of modern alternative treatment with the retention to hold site-specific immune regulation that controls T cells in autoimmune diseases and allograft rejection. The clinical effects of these immune privileged cells need to be further explored, which would have an immense contribution in the field of stem cell therapy.