MSC Dysfunction After HCT Associated With GVHD Onset

By Patrick Daly - Last Updated: November 8, 2022

Data suggest that bone marrow impairment is a major component of prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplant (HCT). Citing the role of mesenchymal stromal cells (MSCs) as progenitors for niche components in bone marrow, researchers investigated the role of MSCs in HCT outcomes, including acute graft-versus-host disease (aGVHD).

In the study, published in Frontiers in Immunology, the authors reported that MSCs were diminished in cases of aGVHD (regardless of bone marrow cellularity), and they did not recover after aGVHD recovery.

Bone Marrow MSCs Diminished Before GVHD Onset

The researchers obtained bone marrow aspirates or biopsies from 73 patients undergoing allogeneic HCT, 18 prior to transplant and 65 after transplant. They quantified functional MSCs using a colony-forming unit fibroblast assay and quantified uncultured MSCs using multicolor flow cytometry.

A total of 39 patients developed aGVHD, and the authors observed a significant decrease in MSC numbers in those patients. Of note, MSC reduction was recorded in 10 patients prior to the clinical onset of aGVHD. In addition, MSC analyses immediately following biopsy collection revealed phenotypic and functional differences depending on the presence of aGVHD; however, these variations disappeared in ex vivo expansion of the samples, the authors reported.

In comparing MSC endotypes, investigators concluded increased donor-derived classical dendritic cells type 1 and alloreactive T cells were the primary drivers of compartmental inflammation and MSC damage prior to aGVHD onset.

Ultimately, the authors suggested that “a reduction in MSCs (or a derailed composition of MSC subtypes) might serve as a surrogate for imminent aGVHD,” though they acknowledged the inherent limitations of their study and called for further research to validate their various findings.

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