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Bains, Amanpreet Kaur [Author]; Behrens Wu, Lena [Author]; Rivière, Jennifer [Author]; Rother, Sandra [Author]; Magno, Valentina [Author]; Friedrichs, Jens [Author]; Werner, Carsten [Author]; Bornhäuser, Martin [Author]; Götze, Katharina S. [Author]; Cross, Michael [Author]; Platzbecker, Uwe [Author]; Wobus, Manja [Author]

Bone marrow mesenchymal stromal cell-derived extracellular matrix displays altered glycosaminoglycan structure and impaired functionality in Myelodysplastic Syndromes

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  • Media type: E-Article
  • Title: Bone marrow mesenchymal stromal cell-derived extracellular matrix displays altered glycosaminoglycan structure and impaired functionality in Myelodysplastic Syndromes
  • Contributor: Bains, Amanpreet Kaur [Author]; Behrens Wu, Lena [Author]; Rivière, Jennifer [Author]; Rother, Sandra [Author]; Magno, Valentina [Author]; Friedrichs, Jens [Author]; Werner, Carsten [Author]; Bornhäuser, Martin [Author]; Götze, Katharina S. [Author]; Cross, Michael [Author]; Platzbecker, Uwe [Author]; Wobus, Manja [Author]
  • Published: Lausanne: Frontiers Media S.A., [2023]
  • Published in: Frontiers in oncology ; 12 (2022), Seite 1-12
  • Language: English
  • DOI: 10.3389/fonc.2022.961473
  • Keywords: mesenchymal stromal cells ; bone marrow ; myelodysplastic syndromes ; extracellular matrix ; hematopoiesis
  • Origination:
  • Footnote:
  • Description: Myelodysplastic syndromes (MDS) comprise a heterogeneous group ofhematologic malignancies characterized by clonal hematopoiesis, one ormore cytopenias such as anemia, neutropenia, or thrombocytopenia,abnormal cellular maturation, and a high risk of progression to acute myeloidleukemia. The bone marrow microenvironment (BMME) in general andmesenchymal stromal cells (MSCs) in particular contribute to both theinitiation and progression of MDS. However, little is known about the role ofMSC-derived extracellularmatrix (ECM) in this context. Therefore, we performeda comparative analysis of in vitro deposited MSC-derived ECM of different MDSsubtypes and healthy controls. Atomic force microscopy analyses demonstratedthat MDS ECM was significantly thicker and more compliant than those fromhealthy MSCs. Scanning electron microscopy showed a dense meshwork offibrillar bundles connected by numerous smaller structures that span thedistance between fibers in MDS ECM. Glycosaminoglycan (GAG) structureswere detectable at high abundance in MDS ECM as white, sponge-like arrayson top of the fibrillar network. Quantification by Blyscan assay confirmed theseobservations, with higher concentrations of sulfated GAGs in MDS ECM.Fluorescent lectin staining with wheat germ agglutinin and peanut agglutinindemonstrated increased deposition of N-acetyl-glucosamine GAGs (hyaluronan(HA) and heparan sulfate) in low risk (LR) MDS ECM. Differential expression of Nacetyl-galactosamine GAGs (chondroitin sulfate, dermatan sulfate) was observedbetween LR- and high risk (HR)-MDS. Moreover, increased amounts of HA in thematrix of MSCs from LR-MDS patients were found to correlate with enhancedHA synthase 1 mRNA expression in these cells. Stimulation of mononuclear cellsfrom healthy donors with low molecular weight HA resulted in an increasedexpression of various pro-inflammatory cytokines suggesting a contribution ofthe ECM to the inflammatory BMME typical of LR-MDS. CD34+ hematopoieticstem and progenitor cells (HSPCs) displayed an impaired differentiation potentialafter cultivation on MDS ECM and modified morphology accompanied bydecreased integrin expression which mediate cell-matrix interaction. Insummary, we provide evidence for structural alterations of the MSC-derivedECM in both LR- and HR-MDS. GAGs may play an important role in thisremodeling processes during the malignant transformation which leads to theobserved disturbance in the support of normal hematopoiesis.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)