Immune system is a highly complex and integrated system of cells, tissues, and organs that have specialized roles in defending against foreign substances and pathogenic micro-organisms, including bacteria, viruses, and fungi. Besides, the immune system also functions to guard against the development of cancer. For these actions, the immune system must recognize foreign invaders as well as abnormal cells and distinguish them from self. As shown in Fig.1, the major components of immune system include skin, lymph nodes, spleen, bone marrow, lymphocytes, thymus, and leukocytes. Among them, the bone marrow is extremely important to the immune system because all the body's blood cells (including T and B lymphocytes) originate in the bone marrow.
Fig.1 Organs of the immune system.
The immune system is a double-edged sword in that host tissues can be damaged in the process of combating and destroying invading pathogens. Immune system disorders cause abnormally overactivity or low activity of the immune system. Types of immune disorder fall into the following three categories.
Induced pluripotent stem cells (iPSCs) can unlimitedly self-renew and differentiate into various cell types. One of the possible applications of iPSCs is its potential use in generating various types of immune cells for immune system disorders therapy. iPSCs provide three potential ways of treating immune system disease, 1) providing pure replacement of lost cells; 2) through immune-modulation of the disease process in vivo; and 3) for disease modeling in vitro. The loss of tolerance to self is the fundamental basis of autoimmunity, with resultant aberrant immune responses of autoantibody formation and/or cellular immunity against self-tissue. There are many important cell populations that impact on systemic autoimmune disease course in which iPSC technology could potentially assist to model their effects and ideally contribute to regaining self-tolerance, such as regulatory T cells (Tregs) and dendritic cells (DCs).
Fig.2 Therapeutic potential of patient-specific iPSCs for the treatment of autoimmune disease. (Son, 2016)
Tregs are CD4, CD25, and Foxp3 positive, and act to restrict the extent and maintain peripheral tolerance by suppressing auto-reactive T cells that have escaped negative selection in the thymus. The ability to induce functional Tregs has been demonstrated from iPSCs in vivo. These cells produced the immunoregulatory cytokines TGFβ and IL-10, thus producing a population of presumably functional Tregs. In a promising find, both allogeneic and autologous transfers of these iPSC derived Tregs demonstrated clinical efficacy in models of RA and SLE.
Numerous abnormalities in DCs have been noted in patients with autoimmune diseases, including variations in cell proportions, differences in cytokine receptor expression, and increased expression of costimulatory molecules. Recently, regulatory DCs have been generated from murine iPSCs. These iPSC-derived regulatory DCs have been shown to have similar morphology and antigen uptake activity to bone marrow-derived regulatory DCs.
Oligodendrocyte precursor cells (OPCs) derived from iPSCs provide an exogenous way in which to remyelinate axons as soon as possible after an episode of acute demyelination, to best protect axons from ongoing inflammation and eventual gliosis. Cell replacement with OPCs derived from iPSCs is successful in animal studies, with remyelination and amelioration of disability in experimental autoimmune encephalitis (EAE), an animal model of MS. Neural precursor cells (NPCs) derived from iPSCs have also been shown in EAE to not only have a regenerative effect, but also an immunomodulatory effect.
Although the present repertoire of immune cells into which they can be differentiated is limited, Creative Biolabs has never stop exploring the iPSC-based regenerative therapy to strategically remove the misguided immune cells and restore normal immune cells to the body. By using disease-specific iPSCs with corresponding genetic features, innate immune cells with pathological features can likely be reproduced. With extensive expertise in iPSC differentiation, Creative Biolabs provides the most flexible, adaptable, and customizable solutions for your project. Contact us for detailed iPSC services.
Reference
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