Impairment of bone marrow endothelial progenitor cells in acute graft‐versus‐host disease patients after allotransplant

Abstract

Graft-versus-host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT) that is frequently associated with bone marrow (BM) suppression, and clinical management is challenging. BM endothelial progenitor cells (EPCs) play crucial roles in the regulation of haematopoiesis and thrombopoiesis. However, little is known regarding the functional roles of BM EPCs in acute GVHD (aGVHD) patients. In the current prospective case-control study, reduced and dysfunctional BM EPCs, characterized by decreased migration and angiogenesis capacities and increased levels of reactive oxygen species (ROS) and apoptosis, were found in aGVHD patients compared with those without aGVHD. Moreover, lower frequency and increased levels of ROS, apoptosis and DNA damage, but reduced colony-forming unit-plating efficiency were found in BM CD34 + cells of aGVHD patients compared with those without aGVHD. The severity of aGVHD and GVHD-mediated cytopenia was associated with BM EPC impairment in aGVHD patients. In addition, the EPC impairment positively correlated with ROS level. Taken together, our results suggest that reduced and dysfunctional BM EPCs may be involved in the pathogenesis of aGVHD. Although these findings require validation, our data indicate that improvement of BM EPCs may represent a promising therapeutic approach for aGVHD patients.

Validation of Housekeeping Genes as Reference for Reverse-Transcription-qPCR Analysis in Busulfan-Injured Microvascular Endothelial Cells

“…The vascular endothelial cells (ECs) are particularly vulnerable to toxic effect of preparative regimen drugs, such as Busulfan, cyclophosphamide, and fludarabine which are widely used prior to hematopoietic stem cell transplantation (HSCT) [ 1 ]. Several studies have indicated that bone marrow (BM) vascular niche was impaired after HSCT [ 2 – 5 ], which was associated with poor Graft Function [ 3 , 4 ]. The healthy ECs, their expressed cytokines, and signal molecules in BM microenvironment play an important role in normal hematopoiesis and repopulation [ 6 – 8 ], while the function of the impaired ECs, the changes of expressed cytokines and signal molecules, and how do these changes affect hematopoietic cell function are still unknown.…”

Hematopoietic Stem Cell Niche During Homeostasis, Malignancy, and Bone Marrow Transplantation

“…After allogeneic hematopoietic stem cell transplantation (also HSCT), the number of EPCs decreased with dysfunction in patients with PGF and aGVHD, manifested as decreased migration and angiogenesis, and increased reactive oxygen levels and apoptosis. The damage degree of EPCs is positively correlated with the level of reactive oxygen species and apoptosis (Kong et al, 2013;Cao et al, 2018).…”

Improved function and balance in T cell modulation by endothelial cells in young people

“…The following multicolour flow cytometry panel were applied to quantify ECs in BM: anti-CD34-PE/Cy7, anti-CD309-PE, and anti-CD133-APC (BD Biosciences, CA, USA). ECs were identified as CD34 + CD309 + CD133 + , and the relative EC frequency was expressed as a fraction of BMMNCs [23][24][25][26][27]. Samples were collected on a BD LSRFortessa flow cytometer and the compensation adjustion as well as data analysis were accomplished via a BD LSRFortessa software.…”