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Heterogeneity of Mesenchymal Stromal Cells in Myelodysplastic Syndrome-with Multilineage Dysplasia (MDS-MLD)

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Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Bone marrow niche constituents have been implicated in the genesis of clonal hematopoietic dysfunction in myelodysplastic syndromes (MDS), though the exact role of stroma in the pathogenesis of MDS remains to be defined. We have evaluated the characteristics of mesenchymal stromal cells in a cohort of patients with MDS with multilineage dysplasia (MDS-MLD). MSCs were cultured from bone marrow aspirates of MDS-MLD patients and controls with healthy bone marrow. Phenotypic characterization, cell cycle, and apoptosis were analyzed by flow cytometry. Targeted gene expression analysis was done using a reverse-transcription polymerase chain reaction (Q-PCR). MSCs derived from MDS patients (MDS-MSCs) showed normal morphology, phenotype, karyotype and differentiation potential towards adipogenic and osteogenic lineages. However, these MDS-MSCs showed significantly altered cell cycle status and displayed a shift towards increased apoptosis compared to control MSCs (C-MSCs). The gene expression profile of niche responsive/regulatory cytokines showed a trend towards lower expression VEGF, SCF, and ANGPT with no changes in expression of CXCL12A and LIF compared to C-MSCs. The expression levels of Notch signaling components like Notch ligands (JAGGED-1 and DELTA-LIKE-1), receptors (NOTCH1, NOTCH3) and downstream gene (HES1) showed an aberrant expression pattern in MDS-MSCs compared to C-MSCs. Similarly, Q-PCR analysis of Wnt signaling inhibitory ligands (DKK-1 and DKK-2) in MDS-MSCs showed a three-fold increase in mRNA expression of DKK1 and a two-fold increase in DKK2 compared to C-MSCs. These data suggested that MDS-MSCs have an altered proliferation characteristic as well as a dysregulated cytokine secretion and signaling profile. These changes could contribute to the pathogenesis of MDS.

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Acknowledgements

We would like to thankfully acknowledge Maulana Azad National Fellowship, University Grants Commission (UGC), Government of India to Salar Abbas. The authors also acknowledge technical support from core facilities of the Centre for Stem Cell Research (CSCR), A unit of the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Government of India.

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Authors and Affiliations

  1. Centre for Stem Cell Research, A Unit of inStem Bengaluru, Christian Medical College Campus, Bagayam, Vellore, Tamil Nadu, 632002, India

    Salar Abbas, Sanjay Kumar & Alok Srivastava

  2. Cytogenetics Unit, Christian Medical College, Vellore, Tamil Nadu, India

    Vivi M. Srivastava

  3. Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India

    Vivi M. Srivastava & Marie Therese M.

  4. Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India

    Sukesh C. Nair

  5. Department of Hematology, Christian Medical College, Vellore, Tamil Nadu, India

    Aby Abraham, Vikram Mathews, Biju George & Alok Srivastava

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  1. Salar Abbas
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  2. Sanjay Kumar
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Correspondence to Alok Srivastava.

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Abbas, S., Kumar, S., Srivastava, V.M. et al. Heterogeneity of Mesenchymal Stromal Cells in Myelodysplastic Syndrome-with Multilineage Dysplasia (MDS-MLD). Indian J Hematol Blood Transfus 35, 223–232 (2019). https://doi.org/10.1007/s12288-018-1062-6

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  • DOI: https://doi.org/10.1007/s12288-018-1062-6

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