Cellular Therapy
Cellular Therapy Targets Immune System and Fibrosis
The rationale of hematopoietic stem cell transplantation (HSCT) is to reset the dysregulated immune system with immunoablative therapy (cytostatic agents, anti-lymphocyte globulin, total body irradiation) followed by reinfusion of previously isolated hematopoietic stem cells. The main mechanism is achieved by eradication of autoaggressive "effector T and B cells" and the induction of regulatory T cells. The idea is to restore tolerance despite the use of autologous cells. With allogenic HSCT, the postulated graft vs autoimmunity effect may contribute to better results but also to more significant side effects. The patients treated with HSCT represent a negative selection of severe cases of short history and involvement of internal organs. Skin thickening and performance status were improved markedly and organ dysfunction stabilized.[104] The early evidence that fibrosis can, in principle, be reversed provides a hopeful outlook for future therapeutic advances.
Abbreviations
SSc, systemic sclerosis; ARA, American Rheumatism Association; ANA, antinuclear antibodies; ACA, anti-centromere antibody; CREST, calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, teleangiectasia; ATA, anti-topoisomerase antibodies; ACE, angiotensin-converting enzyme; MHC, major histocompatibility complex; SNPs, single nucleotide polymorphisms; IRF5, interferon regulatory factor 5; Stat4, signal transducer and activator of transcription 4; PTPN22, protein tyrosine phosphatase, non-receptor type 22; BANK1, B cell scaffold protein with ankyrin repeats 1; CTGF, connective tissue growth factor; TBX21, T-box transcription factor; IL-10R, interleukin 10 receptor; IL-23R, interleukin 23 receptor; TNFSF4, tumor necrosis factor superfamily; PCR, polymerase chain reaction; GvH, graft vs host; TGFβ, transforming growth factor beta; PDGF, platelet-derived growth factor; EC, endothelial cells; NO, nitric oxide; EDRF, endothelial dependent relaxation factor; HIF, hypoxia-induced factor; VEGF, vascular endothelial growth factor; AECA, anti-endothelial cell antibodies; CMV, cytomegalovirus; vWF, von Willebrand factor; IL, interleukin; LFA-1, lymphocyte function-associated antigen 1; BAFF, B cell activating factor; dSSc, diffuse cutaneous SSc; SI-SSc, silica-associated SSc; RNAP, RNA polymerase; MMP, matrix metalloproteinase; ECM, extracellular matrix; PDGFR, platelet derived growth factor receptor; ROS, reactive oxygen species; INF, interferon; TNF-α, tumor necrosis factor-alpha; PN-1, protease nexin-1; AT, angiotensin; PGI2, prostacyclin; PHT, pulmonary hypertension; UVA, ultraviolet A; PUVA, photochemotherapy with UVA; HSCT, hematopoietic stem cell transplantation; Auto-ab, autoantibodies; ADCC, antibody-dependent cell cytotoxicity; TF, tissue factor; VCAM, vascular cell adhesion molecule; ICAM, intercellular adhesion molecule; E-sel, E-selectin; PMNC, polymorphonuclear cells; FB, fibroblast; rec, receptor; ERK 1/2, extracellular-signal-regulated kinases 1 and 2; MCP-1, monocyte chemoattractant protein; TACE, TNF-α converting enzyme; IFN-α interferon-α
Acknowledgements
I am very grateful to Walter Burgdorf, PhD, (Tutzing) and Ulf Anderegg, PhD, (Leipzig) for their competent help; to Ilona Dobbert (Leipzig) for review of the references; and to Raik Tilitzki (Leipzig) for his excellent technical assistance.
Lab Med. 2011;42(9):562-572. © 2011 American Society for Clinical Pathology
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