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

Atmar, Khaled; Tulling, Adam  J.; Lankester, Arjan C.; Bartels, Marije; Smiers, Frans J.; Burg, Mirjam van der; Mohseny, Alexander B.

doi:10.3389/fimmu.2022.859668

Cited by 6 publications

(4 citation statements)

References 69 publications

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“…Using their basic properties as indicators, we firstly documented lower potential of proliferation and differentiation in SAA MSCs without changes in their morphologies and surface marker expressions [ 8 ]. Since then, these characteristics of SAA MSCs have been investigated in a number of studies [ 18 ]. The majority indicated worse proliferative ability of SAA MSCs, and all studies demonstrated no difference in their surface marker expression.…”

Section: Discussionmentioning

confidence: 99%

Alterations of mesenchymal stem cells on regulating Th17 and Treg differentiation in severe aplastic anemia

Chao

et al. 2023

Aging

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Immune-mediated hematopoietic destruction is a key factor in idiopathic severe aplastic anemia (SAA). With great immunomodulatory functions, mesenchymal stem cells (MSCs) are important for bone marrow niche. While the underlying etiology of immunologic changes in SAA bone marrow remains unknown, dysfunctional MSCs are implicated as a major cause. To provide evidence for their defects in immunomodulation, alterations of SAA MSCs in regulating T cell differentiation were determined. During differentiation from CD4+ T cells into T helper 17 (Th17) cells under polarization conditions, impaired inhibition on IL-17 and IL-1β production was noted when cocultured with SAA MSCs compared to control MSCs (P < 0.05). After stimulation of Th17 activation, the percentage of IL-17-secreting cells was significantly increased in the SAA group (9.1 ± 1.5% vs 6.6 ± 0.4%, P < 0.01). Under regulatory T (Treg) polarization, a higher percentage of CD4+CD25+FoxP3+ Treg cells was detected when cocultured with SAA MSCs compared to control MSCs (8.1 ± 0.5% vs 5.8 ± 0.8%, P < 0.01). Inconsistently, transforming growth factor-β (TGF-β) concentrations in the culture supernatant were decreased and IL-1β concentrations were elevated in the SAA group. Our data indicated impaired inhibition of SAA MSCs on Th17 activation and aberrant regulation of SAA MSCs on Treg differentiation. Increased IL-17 and IL-1β levels with decreased TGF-β levels in the supernatant suggested the potential of SAA MSCs for triggering a hyperinflammatory environment. Dysfunctional MSCs could contribute to the lack of immunoprotection in the bone marrow, which may be associated with SAA.

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Section: Discussionmentioning

confidence: 99%

Alterations of mesenchymal stem cells on regulating Th17 and Treg differentiation in severe aplastic anemia

Chao

et al. 2023

Aging

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“…Among multiple studied factors, the dysfunction of BM environment and mesenchymal stromal cell dysregulation might contribute to the damage in the stem-cell niche (9). Immune pressure from T-cell-mediated mechanisms leads to somatic gene alterations in HSCs, resulting in immune evasion (10).…”

Section: Pathophysiology and Clonal Evolutionmentioning

confidence: 99%

“…Haploidentical HCT with CD45RA (4 patients), TCRab-CD19 depletion or PTCy (5 patients) was evaluated in 11 patients with SAA or MDS-refractory cytopenia of childhood (212). The conditioning regimens were heterogenous and consisted of Flu combined with irradiation techniques (9), Cy (9), busulfan, treosulfan, or thiotepa. Despite engraftment, 2 patients died, and 4 of 9 long-term survivors developed cGVHD.…”

Section: Haploidentical Hctmentioning

confidence: 99%

The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults

Piekarska,

Pawelec,

Szmigielska-Kapłon

et al. 2024

Front. Immunol.

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Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell–mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient’s age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies.

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“…Mostly, Aplastic anemia (AA) patients have pancytopenia, with decreased levels of platelets and white blood cells 1 , 2 . The immune function of AA patients is always low, which makes AA patients susceptible to infection, and infection is also a significant cause of death in AA patients 3 , 4 . Infection, especially early pulmonary infection, has always been a fundamental problem for hematologists, mainly because pulmonary infection, especially early infection, is not easy to diagnose.…”

Section: Introductionmentioning

confidence: 99%

Cytokines help suggest aplastic anemia with pulmonary bacterial or co-fungal infection

Zhang

Yang

et al. 2022

Sci Rep

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Although aplastic anemia (AA) does not come under the category of blood malignant diseases, the infection that frequently occurs in this bone marrow failure can make it worse. Pulmonary infection is the most prevalent but limiting clinical diagnosis. To find biomarkers predicting bacterial or bacterial-combined fungal infections in the lungs, we reviewed 287 AA medical records including 151 without any infection, 87 with pure pulmonary bacterial infection, and 49 with bacterial and fungal infection were reviewed. There were substantial changes in IL-17F, IL-17A, IFN-γ, IL-6, IL-8, and IL-10 levels between the non-infected and lung bacterial infection groups (P < 0.05). Further, a significant variation in IL-17A, TNF-β, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-22, and IL-12p70, between the uninfected group and the pulmonary bacterial and fungal infection group (P < 0.05) was observed. The results further revealed significant differences in TNF-β, IL-12p70, IL-6, IL-8, and IL-10 between the pulmonary bacterial infection group and the fungal infection group (P < 0.05). Moreover, by calculating ROC and cut-off values, we determined that IL-6 (AUC = 0.98, Cut-off = 14.28 pg/ml, P = 0.0000) had a significant advantage than other cytokines, body temperature (AUC = 0.61, P = 0.0050), PCT (AUC = 0.57, P = 0.0592), and CRP (AUC = 0.60, P = 0.0147) in the detection of lungs bacterial infections. In addition, IL-6 (AUC = 1.00, Cut-off = 51.50 pg/ml, P = 0.000) and IL-8 (AUC = 0.87, Cut-off = 60.53 pg/ml, P = 0.0000) showed stronger advantages than other cytokines, body temperature (AUC = 0.60, P = 0.0324), PCT (AUC = 0.72, Cut-off = 0.63 ng/ml, P = 0.0000) and CRP (AUC = 0.79, Cut-off = 5.79 mg/l, P = 0.0000) in distinguishing bacteria from fungi. This may suggest that IL-8 may play a role in differentiating co-infected bacteria and fungi. Such advantages are repeated in severe aplastic anemia (SAA) and very severe aplastic anemia (VSAA).In conclusion, aberrant IL-6 elevations in AA patients may predict the likelihood of bacterial lung infection. The concurrent increase of IL-6 and IL-8, on the other hand, should signal bacterial and fungal infections in patients.These findings may help to suggest bacterial or fungal co-infection in patients with AA (Focus on VSAA and SAA).

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

Cited by 6 publications

References 69 publications

Alterations of mesenchymal stem cells on regulating Th17 and Treg differentiation in severe aplastic anemia

Alterations of mesenchymal stem cells on regulating Th17 and Treg differentiation in severe aplastic anemia

The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults

Cytokines help suggest aplastic anemia with pulmonary bacterial or co-fungal infection

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