Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications

Abstract

Extracellular vesicles (EVs) play an important role in the cellular crosstalk by transferring bioactive molecules through biological barriers from a cell to another, thus influencing recipient cell functions and phenotype. Therefore, EVs are increasingly being explored as biomarkers of disease progression or response to therapy and as potential therapeutic agents in different contexts including in hematological malignancies. Recently, an EV role has emerged in allogeneic hematopoietic cell transplantation (allo-HCT) as well. Allogeneic hematopoietic cell transplantation often represents the only curative option in several hematological disorders, but it is associated with potentially life-threatening complications that can have a significant impact on clinical outcomes. The most common complications have been well-established and include graft-versus-host disease and infections. Furthermore, relapse remains an important cause of treatment failure. The aim of this review is to summarize the current knowledge, the potential applications, and clinical relevance of EVs in allo-HCT. Herein, we will mainly focus on the immune-modulating properties of EVs, in particular those derived from mesenchymal stromal cells, as potential therapeutic strategy to improve allo-HCT outcome. Moreover, we will briefly describe the main findings on EVs as biomarkers to monitor graft-versushost disease onset and tumor relapse.

Improving hematopoietic engraftment: Potential role of mesenchymal stromal cell-derived extracellular vesicles

“…47 Thus, MSC-EVs could have a beneficial effect in the hematopoietic transplantation setting. 18,48 It has been also demonstrated that MSC-EVs exert immunomodulatory effects on T cells in vitro and anti-GVHD effects in mice. 42,49 Regarding homing and engraftment, both murine and human MSC-EVs can improve the engraftment of CD34 + cells previously damaged by irradiation.…”

“…In preclinical studies in different disease models, MSC‐EVs are able to exert immunomodulatory (reducing pro‐inflammatory cytokine response and increasing the production of anti‐inflammatory cytokines) 16,35 and tissue repairing effects (protecting against ischemia‐reperfusion‐induced acute chronic kidney injury or reducing myocardial ischemia) 46 and to favor hematopoietic cell maintenance 47 . Thus, MSC‐EVs could have a beneficial effect in the hematopoietic transplantation setting 18,48 . It has been also demonstrated that MSC‐EVs exert immunomodulatory effects on T cells in vitro and anti‐GVHD effects in mice 42,49 .…”

Immunomodulatory and clinical effects of daratumumab in T‐cell acute lymphoblastic leukaemia

“…Functional assays were employed to assess the granzyme and perforin cytotoxic molecules on T cells. Analysis of CD38 release in Extracellular Vesicles (EVs) was performed as previously described 11 (see also Appendix S1).…”

Preclinical Studies of MSC-Derived Extracellular Vesicles to Treat or Prevent Graft Versus Host Disease: a Systematic Review of the Literature

“…Large EVs (150 – 1000 nm [ 17 ]), or microvesicles, are formed by outward budding of the plasma membrane and contain contents of the cytoplasm that are distinct from small EVs and may serve as biomarkers of cellular stress rather than effectors of immune modulation. Indeed, MSC-derived microvesicles have demonstrated promise as biomarkers of GVHD [ 29 , 30 ]. Isolation methods such as centrifugation may yield MSC-derived products with a mixture of small and large EVs.…”