Transplantation of Genetically Modified Haematopoietic Stem Cells to Induce Antigen-Specific Tolerance as a Cure for Autoimmune Diseases
Autoimmune diseases are incurable and are managed using therapeutic agents. Bone marrow transplantation is being trialled as a treatment for these diseases. While allogeneic bone marrow transplantation shows impressive benefit, its application is hindered by GVHD and high mortality. On the other hand, autologous bone marrow transplantation has lower mortality rate and no GVHD but is associated with higher relapse rates. Given that autoimmune diseases are a result of a failure of immune tolerance and that bone marrow-derived dendritic cells play an important role in establishing immune tolerance, the transplantation of genetically modified haematopoietic stem cells to generate molecular chimerism to induce antigen-specific tolerance offers the potential for developing a cure for autoimmune diseases. In this review, we will discuss key findings from clinical data and animal studies to provide evidence to support the above concept.
Keywords: Autoimmune diseases, transplantation, haematopoietic stem cells, immune tolerance, dendritic cells, tissue repair, Bone marrow transplantation, chimerism, antigen-specific tolerance, Autoimmune diseases,, systemic lupus erythe-matosus, type 1 diabetes, rheumatoid arthritis, multiple sclerosis, adaptive immune system, leucocyte, cytokine, leukemia, aplastic anemia, thyroiditis, myasthenia gravis, lymphocytes, thymus, spleen, apoptosis, AIRE (Autoimmune Regulator Element), graft-versus-host disease, regulatory T cells (Treg), Foxp3- T cells, myelin oligodendrocyte glycopro-tein, induced experimental autoimmune encephalo-myelitis, proinsulin II, 2D2 thymocytes, CD4 T cells, progenitor cells, inflammatory infiltrate, methylprednisolone, microenvironment, inflammatory cells, pathogenesis
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