Impaired immunomodulatory ability of bone marrow mesenchymal stem cells on CD4+ T cells in aplastic anemia

Abstract

Aplastic anemia (AA) is a marrow failure syndrome mediated by aberrant T-cell subsets. Mesenchymal stem cells (MSCs) play an important role in maintaining immune homeostasis through modulating a variety of immune cells. However, little is known about the immunomodulation potential of bone marrow MSCs (BM-MSCs) in AA. Here, we reported that BM-MSCs from AA patients were reduced in suppressing the proliferation and clonogenic potential of CD4(+) T cells and the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which was associated with decreased prostaglandin E2 (PGE2). Meanwhile, BM-MSCs from AA patients were defective to promote CD4(+)CD25(+)FOXP3(+) regulatory T cells expansion through reduced transforming growth factor-β (TGF-β). No significant difference between AA and normal BM-MSCs was observed in affecting the production of interleukins (IL)-4, IL-10 and IL-17. Our data indicate that BM-MSCs were impaired in maintaining the immune homeostasis associated with CD4(+) T cells, which might aggravate the marrow failure in AA.

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

“…The median TTR of leukocytic linage was 19 days (range, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The median TTR of erythrocytic linage was 17 days (range, [12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Differential Gene Expression Profile Associated with the Abnormality of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

“…We found that BM-MSCs from AA patients had reduced potential to amplify CD34 + cells and support the process of megakaryocytopoiesis. BM-MSCs from AA patients were reduced in suppressing the proliferation potential of CD4 + cells, TNF-α and IFN-γ production by CD4 + cells, and promoting Tregs expansion [25]. When BM-MSCs were damaged and became defective, the bone marrow suffered more severe losses in maintaining immune homeostasis which further aggravated the aberrant immunity in AA.…”

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…Aplastic anemia was originally suggested to be a primary HSC deficiency or a secondary HSC defect due to an abnormal balance between cellular death and differentiation [128]. However, MSCs as marrow microenvironment cells may also play an important role in the development of the disease by causing an imbalance in immune regulation and aggravating bone marrow failure [129]. …”