Human Acquired Aplastic Anemia Patients’ Bone-Marrow-Derived Mesenchymal Stem Cells Are Not Influenced by Hematopoietic Compartment and Maintain Stemness and Immune Properties

Abstract

Background and Objective. Acquired aplastic anemia (aAA) is a bone marrow failure disorder characterized by pancytopenia and bone marrow aplasia. Bone marrow Mesenchymal Stem Cells (BM-MSCs) are an important component of BM microenvironment, associated with hematopoietic and immune homeostasis. Any alterations in BM microenvironment can disrupt the normal functioning and it needs to be assessed. Methods. In the current study, we investigated the morphological differences, proliferation capacity, population doubling time (PDT), surface marker profiling, trilineage differentiation potential, and immunosuppressive ability of BM Mesenchymal Stem Cells (BM-MSCs) from untreated aAA patients and in the same number of age- and gender-matched controls. Results. We observed similar morphology, proliferation capacity, phenotype, trilineage differentiation potential, and immunomodulatory properties of BM-MSCs in aAA patients and control subjects. Conclusion. Our results confirm that the basic and immunosuppressive properties of BM-MSCs from aAA patients do not differ from normal BM-MSCs. Our data suggest that BM-MSCs from aAA patients might not be involved in disease pathogenesis. However, owing to a smaller number of samples, it is not conclusive, and future studies with more exhaustive investigation at transcriptome level are warranted.

Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells

“…[11][12][13] In addition, MSCs may be altered in severe aplastic anemia patients, although the results are controversial. [14][15][16] These suggested alterations in MSCs from patients with ITP or AA make it even more worthwhile to evaluate the effects of EP on healthy-donor-derived MSCs.…”

Functional and Immune Modulatory Characteristics of Bone Marrow Mesenchymal Stromal Cells in Patients With Aplastic Anemia: A Systematic Review

“…This has been examined in 5 studies using the colony forming unit-fibroblast assay ( 33 , 36 , 43 , 45 , 47 ) ( Table 6 ). Whereas the majority of studies (8/11) indicated worse proliferation and clonogenic ability of AA-MSC compared to control-MSC, others (2/11) did not observe a difference ( 25 , 47 ). In a single study the opposite result was found ( 45 ).…”

“…Qualitative methods to measure chondrogenic differentiation potential included Alcian Blue staining in addition to RT-qPCR as a quantitative measurement method. 2/4 studies found no difference in chondrogenic differentiation tendency ( 25 , 33 ) while one study observed lower chondrogenic potency in AA-MSCs ( 29 ). As indicated previously no information could be deduced from the study by Bacigalupo et al.…”

“…This is in line with the findings of Li et al (43) in which T cells were less likely to differentiate towards regulatory T-cells. In two studies no difference could be detected between both groups (25,37). In contrast, a single study observed that AA-patient derived MSCs were even more able to suppress proliferation of PHA-activated peripheral bone marrow mononuclear cells (PBMCs) as compared to healthy MSCs (30).…”

“…Of these three studies only one used a quantitative method (44). Finally, no difference was detected between AA-MSCs and control MSCs in three studies (25,33,37)…”