Bone marrow niche in immune thrombocytopenia: a focus on megakaryopoiesis

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased bleeding tendency and thrombocytopenia. In fact, the precise pathogenesis of this disease is still not clear. Megakaryopoiesis involves complete differentiation of megakaryocyte (MK) progenitors to functional platelets. This complex process occurs in specific bone marrow (BM) niches composed of several hematopoietic and non-hematopoietic cell types, soluble factors, and extracellular matrix proteins. These specialized microenvironments sustain MK maturation and localization to sinusoids as well as platelet release into circulation. However, MKs in ITP patients show impaired maturation and signs of degradation. Intrinsic defects in MKs and their extrinsic environment have been implicated in altered megakaryopoiesis in this disease. In particular, aberrant expression of miRNAs directing MK proliferation, differentiation, and platelet production; defective MK apoptosis; and reduced proliferation and differentiation rate of the MSC compartment observed in these patients may account for BM defects in ITP. Furthermore, insufficient production of thrombopoietin is another likely reason for ITP development. Therefore, identifying the signaling pathways and transcription factors influencing the interaction between MKs and BM niche in ITP patients will contribute to increased platelet production in order to prevent incomplete MK maturation and destruction as well as BM fibrosis and apoptosis in ITP. In this review, we will examine the interaction and role of BM niches in orchestrating megakaryopoiesis in ITP patients and discuss how these factors can be exploited to improve the quality of patient treatment and prognosis.

A silk fibroin/decellularized extract of Wharton’s jelly hydrogel intended for cartilage tissue engineering

“…It is known that there is a broad range of interactions between MSCs and their environment which means that the niche or microenvironment of these cells is vital for supporting and stimulating them to do their functions well (Khodadi et al 2016; Sobolewski et al 2005). Previous studies have shown the considerable effects of WJ-MSCs conditioned medium on up-regulation of several factors which assist in wound healing and increasing human skin fibroblasts expansion and migration in vivo (Arno et al 2014).…”

Splenectomy for immune thrombocytopenia: down but not out

“…1 ITP occurs either as a primary disorder or secondary to underlying neoplasia, infection, or autoimmune disease; in the latter case there may be more profound immune dysregulation. 2 The spleen plays a critical role in the pathogenesis of ITP ( Figure 1).…”

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

“…ITP involves isolated thrombocytopenia [4] as a result of anti-platelet antibody production by plasma cells that induce antibody-mediated platelet phagocytosis [5, 6], T-cell mediated platelet destruction [7], and/or impairment of megakaryocyte function [8-10]. In recent years, immune dysregulation due to ITP, especially cellular immune deficiency, has been an active area of research [11].…”