Innovative strategies for immune thrombocytopenia treatment: immunomodulatory mechanisms and clinical potential of mesenchymal stem cells

Abstract

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by increased platelet destruction and impaired megakaryopoiesis within a dysregulated bone marrow niche. Conventional therapies often achieve only transient platelet recovery, failing to restore immune tolerance, thereby underscoring the need for mechanism-based therapeutic strategies. Mesenchymal stem cells (MSCs) have emerged as promising candidates due to their ability to modulate immune responses and repair the hematopoietic microenvironment. This review synthesizes current evidence regarding the biological properties, immunomodulatory mechanisms, and therapeutic applications of MSCs in ITP, emphasizing intrinsic abnormalities of patient-derived MSCs and the corrective potential of exogenous MSCs from distinct tissue sources. It further integrates emerging insights into MSC functional heterogeneity, optimization of culture conditions, priming strategies, and cellular engineering approaches that may enhance therapeutic efficacy and safety. By highlighting the interplay between immune tolerance restoration and bone marrow niche remodeling, this review provides a translational framework that links mechanistic understanding to the future clinical development of MSC-based therapies for ITP.

1. Introduction

Immune thrombocytopenia (ITP) is an autoimmune blood disorder defined by platelet counts below 100×10^9/L, leading to an increased risk of bleeding. The primary pathogenic mechanism involves the breakdown of immune tolerance, predominantly driven by impaired function of regulatory cells, including Tregs, Bregs, and myeloid-derived suppressor cells. Consequently, when this regulatory network is compromised, autoreactive immune cells become activated, producing anti-platelet antibodies and cytotoxic T cells, which simultaneously destroy circulating platelets and inhibit platelet production in the bone marrow. These insights into the underlying mechanisms of ITP underscore the necessity for treatments specifically targeting these pathological processes to achieve sustained responses and improved quality of life.

MSCs, particularly bone marrow-derived MSCs (BMSCs), are multipotent stromal cells known for their immunomodulatory properties across various diseases. Recent evidence highlights their crucial involvement in ITP pathogenesis, in which impaired BMSCs exhibit deficient regulation of macrophage polarization, a key mechanism in the immune dysregulation observed in ITP. Studies indicate that BMSC administration can effectively correct the imbalance between M1/M2 macrophages, reduce proinflammatory cytokine levels, and subsequently increase platelet counts in ITP model. Furthermore, the HMGB1-TLR4 pathway has been identified as a potential therapeutic target to restore the immunoregulatory function of BMSCs in ITP. This review comprehensively examines the pathophysiological and therapeutic roles of MSCs in ITP, highlighting their potential as a novel treatment strategy for this complex autoimmune disorder.